Journal of Pathology and Translational Medicine

Original Articles

MicroRNA-552 expression in colorectal cancer and its clinicopathological significance: Joon Im, Soo Kyung Nam, Hye Seung Lee; J Pathol Transl Med. 2021;55(2):125-131. Published online February 19, 2021; DOI: https://doi.org/10.4132/jptm.2021.01.17

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Background
MicroRNA-552 (miR-552) has been reported to correlate with the development and progression of various cancers, including colorectal cancer (CRC). This study aimed to investigate miR-552 expression in cancer tissue samples compared to normal mucosal tissue and its role as a diagnostic or prognostic marker in CRC patients.
Methods
Normal mucosal tissues and primary cancer tissues from 80 surgically resected CRC specimens were used. Quantitative real-time polymerase chain reaction was performed for miR-552 and U6 small nuclear RNA to analyze miR-552 expression and its clinicopathological significance. Immunohistochemistry for p53 and phosphatase and tension homolog (PTEN) was performed to evaluate their association with miR-552 expression.
Results
miR-552 expression was significantly higher in primary cancer tissues compared to normal mucosal tissues (p<.001). The expression level of miR552 was inversely correlated with that of PTEN (p=.068) and p53 (p=.004). Survival analysis showed that high miR-552 expression was associated with worse prognosis but this was not statistically significant (p=.255). However, patients with CRC having high miR-552 expression and loss of PTEN expression had significantly worse prognosis than others (p=.029).
Conclusions
Our results suggest that high miR-552 expression might be a potential diagnostic biomarker for CRC, and its combined analysis with PTEN expression can possibly be used as a prognostic marker.

Citations

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MicroRNAs involved in colorectal cancer, a rapid mini-systematic review
Sogol Shirzad, Majid Eterafi, Zeinab Karimi, Mahdi Barazesh
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Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer: Hye Jung Hwang, Soo Kyung Nam, Hyunjin Park, Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Woo Ho Kim, Hye Seung Lee; J Pathol Transl Med. 2020;54(5):378-386. Published online July 1, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.01

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Abstract PDF Supplementary Material

Background
Recently, molecular classifications of gastric cancer (GC) have been proposed that include TP53 mutations and their functional activity. We aimed to demonstrate the correlation between p53 immunohistochemistry (IHC) and TP53 mutations as well as their clinicopathological significance in GC.
Methods
Deep targeted sequencing was performed using surgical or biopsy specimens from 120 patients with GC. IHC for p53 was performed and interpreted as strong, weak, or negative expression. In 18 cases (15.0%) with discrepant TP53 mutation and p53 IHC results, p53 IHC was repeated.
Results
Strong expression of p53 was associated with TP53 missense mutations, negative expression with other types of mutations, and weak expression with wild-type TP53 (p<.001). The sensitivity for each category was 90.9%, 79.0%, and 80.9%, and the specificity was 95.4%, 88.1%, and 92.3%, respectively. The TNM stage at initial diagnosis exhibited a significant correlation with both TP53 mutation type (p=.004) and p53 expression status (p=.029). The Kaplan-Meier survival analysis for 109 stage II and III GC cases showed that patients with TP53 missense mutations had worse overall survival than those in the wild-type and other mutation groups (p=.028). Strong expression of p53 was also associated with worse overall survival in comparison to negative and weak expression (p=.035).
Conclusions
Results of IHC of the p53 protein may be used as a simple surrogate marker of TP53 mutations. However, negative expression of p53 and other types of mutations of TP53 should be carefully interpreted because of its lower sensitivity and different prognostic implications.

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Molecular and Clinicopathological Features of Gastrointestinal Stromal Tumors in Vietnamese Patients: Quoc Dat Ngo, Quoc Thang Pham, Dang Anh Thu Phan, Anh Vu Hoang, Thi Ngoc Ha Hua, Sao Trung Nguyen; J Pathol Transl Med. 2019;53(6):361-368. Published online September 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.08.27

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Abstract PDF Supplementary Material

Background
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.
Methods
We first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.
Results
The largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.
Conclusions
The expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.

Citations

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Ki67 for evaluating the prognosis of gastrointestinal stromal tumors: A systematic review and meta‑analysis
Ji Li, An-Ran Wang, Xiao-Dong Chen, Hong Pan, Shi-Qiang Li
Oncology Letters.2022;[Epub] CrossRef
Endoscopic ultrasound‐guided fine‐needle aspiration cytology in the diagnosis of the gastrointestinal stromal tumor of the stomach
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Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects: Natalia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Artem Piddubnyi, Ludmila Karpenko, Olha Kravtsova, Dmytrii Hyriavenko, Olena Diachenko, Vladyslav Sikora, Anatolii Romaniuk; J Pathol Transl Med. 2019;53(4):236-243. Published online April 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.21

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Abstract PDF

Background
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods
The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results
ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions
Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.

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D.G. Sumtsov, G.O. Sumtsov, N.I. Hyriavenko, S.A. Smiian, N.V. Kalashnyk, K.O. Sikora, N.M. Rozhkovska, I.Z. Gladchuk
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Association between Expression of 8-OHdG and Cigarette Smoking in Non-small Cell Lung Cancer: Ae Ri An, Kyoung Min Kim, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Yong Chul Lee, Jong Hun Kim, Han Jung Chae, Myoung Ja Chung; J Pathol Transl Med. 2019;53(4):217-224. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.20

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Abstract PDF

Background
Exposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC).
Methods
We investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking.
Results
The expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05).
Conclusions
The expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.

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Didem ÖZKAL EMİNOĞLU, Varol ÇANAKÇI
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Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Miseon Lee, In Ah Park, Sun-Hee Heo, Young-Ae Kim, Gyungyub Gong, Hee Jin Lee; J Pathol Transl Med. 2019;53(3):180-187. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.08

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Abstract PDF

Background
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
Methods
In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
Results
No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
Conclusions
High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.

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Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics: Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim; J Pathol Transl Med. 2019;53(1):31-39. Published online December 18, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.16

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Abstract PDF

Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT.

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Boubacar Efared, Halidou Hamadou Koura, Aïchatou Balaraba Abani Bako, Idrissa Boubacar, Habiba Salifou Boureima, Garba Mahamadou, Hassan Nouhou
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Uterine carcinosarcoma: Unraveling the role of epithelial‐to‐mesenchymal transition in progression and therapeutic potential
Mohan Shankar Gopinatha Pillai, Pallab Shaw, Arpan Dey Bhowmik, Resham Bhattacharya, Geeta Rao, Shailendra Kumar Dhar Dwivedi
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Tamoxifen/toremifene

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Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
Susanna Leskela, Belen Pérez-Mies, Juan Manuel Rosa-Rosa, Eva Cristobal, Michele Biscuola, María L. Palacios-Berraquero, SuFey Ong, Xavier Matias-Guiu Guia, José Palacios
Cancers.2019; 11(7): 964. CrossRef

Basaloid Squamous Cell Carcinoma of the Head and Neck: Subclassification into Basal, Ductal, and Mixed Subtypes Based on Comparison of Clinico-pathologic Features and Expression of p53, Cyclin D1, Epidermal Growth Factor Receptor, p16, and Human Papillomavirus: Kyung-Ja Cho, Se Un Jeong, Sung Bae Kim, Sang-wook Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim; J Pathol Transl Med. 2017;51(4):374-380. Published online June 8, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.03

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Abstract PDF

Background
Basaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma with distinct pathologic characteristics. The histogenesis of BSCC is not fully understood, and the cancer has been suggested to originate from a totipotent primitive cell in the basal cell layer of the surface epithelium or in the proximal duct of secretory glands.
Methods
Twenty-six cases of head and neck BSCC from Asan Medical Center, Seoul, Korea, reported during a 14-year-period were subclassified into basal, ductal, and mixed subtypes according to the expression of basal (cytokeratin [CK] 5/6, p63) or ductal markers (CK7, CK8/18). The cases were also subject to immunohistochemical study for CK19, p53, cyclin D1, epidermal growth factor receptor (EGFR), and p16 and to in situ hybridization for human papillomavirus (HPV), and the results were clinico-pathologically compared.
Results
Mixed subtype (12 cases) was the most common, and these cases showed hypopharyngeal predilection, older age, and higher expression of CK19, p53, and EGFR than other subtypes. The basal subtype (nine cases) showed frequent comedo-necrosis and high expression of cyclin D1. The ductal subtype (five cases) showed the lowest expression of p53, cyclin D1, and EGFR. A small number of p16- and/or HPV-positive cases were not restricted to one subtype. BSCC was the cause of death in 19 patients, and the average follow-up period for all patients was 79.5 months. Overall survival among the three subtypes was not significantly different.
Conclusions
The results of this study suggest a heterogeneous pathogenesis of head and neck BSCC. Each subtype showed variable histology and immunoprofiles, although the clinical implication of heterogeneity was not determined in this study.

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Histopathological variants of head and neck squamous cell carcinomas: A multicenter study in Latin America
Heitor Albergoni Silveira, Karina Helen Martins, Ana Lia Anbinder, Thais Aguiar Santos, Elton Fernandes Barros, Pollianna Muniz Alves, Cassiano Francisco Weege Nonaka, Ana Terezinha Marques Mesquita, Matheus Henrique Lopes Dominguete, Rafael Rodrigues Dia
Annals of Diagnostic Pathology.2026; 80: 152565. CrossRef
HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management
Matt Lechner, Jacklyn Liu, Liam Masterson, Tim R. Fenton
Nature Reviews Clinical Oncology.2022; 19(5): 306. CrossRef
Neoadjuvant treatment combined with planned endoscopic surgery in locally advanced sphenoid sinus basaloid squamous cell carcinoma
Yinghong Zhang, Suqing Tian, Yali Du, Qiang Zuo, Li Zhu, Furong Ma
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Cetuximab and paclitaxel combination therapy for recurrent basaloid squamous cell carcinoma in the ethmoid sinus
Satoshi Koyama, Kazunori Fujiwara, Tsuyoshi Morisaki, Taihei Fujii, Yosuke Nakamura, Takahiro Fukuhara, Hiromi Takeuchi
Auris Nasus Larynx.2021; 48(6): 1189. CrossRef
Constitutive Hedgehog/GLI2 signaling drives extracutaneous basaloid squamous cell carcinoma development and bone remodeling
Marina Grachtchouk, Jianhong Liu, Mark E Hutchin, Paul W Harms, Dafydd Thomas, Lebing Wei, Aiqin Wang, Donelle Cummings, Lori Lowe, Jonathan Garlick, James Sciubba, Arul M Chinnaiyan, Monique E Verhaegen, Andrzej A Dlugosz
Carcinogenesis.2021; 42(8): 1100. CrossRef
Conjunctival ‘mucoepidermoid carcinoma’ revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye
Hardeep S. Mudhar, Tatyana Milman, Paul J.L. Zhang, Carol L. Shields, Ralph C. Eagle, Sara E. Lally, Jerry A. Shields, Sachin M. Salvi, Paul A. Rundle, Jennifer Tan, Ian G. Rennie
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Basaloid squamous cell carcinoma with adenoid cystic‐like features of the head and neck region: A report of two cases
Kimihide Kusafuka, Haruna Yagi, Satoshi Baba, Hiroshi Inagaki, Chinatsu Tsuchiya, Kazuki Hirata, Aya Muramatsu, Makoto Suzuki, Kazumori Arai, Tadashi Terada
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Lifang Cui, Congling Qu, Honggang Liu
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The Korean Journal of Oral and Maxillofacial Pathology.2019; 43(5): 197. CrossRef
p53 and p16 expression in oral cavity squamous cell and basaloid squamous cell carcinoma
Allisson Filipe Lopes Martins, Carlos Henrique Pereira, Marília Oliveira Morais, Paulo Otávio Carmo Souza, Lucas Borges Fleury Fernandes, Aline Carvalho Batista, Elismauro Francisco Mendonça
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The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence: Jee Soon Kim, Youn Soo Lee, Min Jung Jung, Yong Kil Hong; J Pathol Transl Med. 2016;50(6):419-425. Published online October 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.30

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Abstract PDF

Background
The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.
Methods
One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.
Results
Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).
Conclusions
Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

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Marta Araujo-Castro, Víctor Rodríguez Berrocal, Eider Pascual-Corrales
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E. Guadagno, E. D’Avella, P. Cappabianca, A. Colao, M. Del Basso De Caro
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Pavel V. Nikitin, Marina V. Ryzhova, Lyudmila V. Shishkina, Svetlana V. Shugay, Irina V. Zubova
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The Role of TWIST in Ovarian Epithelial Cancers: Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi; Korean J Pathol. 2014;48(4):283-291. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.283

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Abstract PDF

Background

Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.

Methods

We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.

Results

The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.

Conclusions

Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

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Pande Kadek Aditya Prayudi, I Gde Sastra Winata, I Nyoman Bayu Mahendra, I Nyoman Gede Budiana, Kade Yudi Saspriyana, Ketut Suwiyoga
Clinical and Experimental Obstetrics & Gynecology.2023;[Epub] CrossRef
E-Cadherin Expression in Relation to Clinicopathological Parameters and Survival of Patients with Epithelial Ovarian Cancer
Michal Kielbik, Izabela Szulc-Kielbik, Magdalena Klink
International Journal of Molecular Sciences.2022; 23(22): 14383. CrossRef
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Pawel Sadlecki, Jakub Jóźwicki, Paulina Antosik, Marek Grabiec
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Expression and prognostic significance of epithelial-mesenchymal transition-related markers and phenotype in serous ovarian cancer
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Transcription factors controlling E-cadherin down-regulation in ovarian cancer
Holly Russell, Md Zahidul Islam Pranjol
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Immunohistochemical expression of TWIST in oral squamous cell carcinoma and its correlation with clinicopathologic factors
Maryam Seyedmajidi, Safoura Seifi, Dariush Moslemi, Seyyedeh-Fatemeh Mozaffari, Hemmat Gholinia, Zahra Zolfaghari
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Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression
Yi‐Hui Wu, Yu‐Fang Huang, Tzu‐Hao Chang, Cheng‐Yang Chou
International Journal of Cancer.2017; 141(11): 2305. CrossRef
MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway
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IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma: Ji Young Park, Misun Choe, Yuna Kang, Sang Sook Lee; Korean J Pathol. 2014;48(2):108-116. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.108

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Abstract PDF

Background

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes.

Methods

We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed.

Results

Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival.

Conclusions

IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.

Citations

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IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas
Natividad Martin-Morales, Miguel Padial-Molina, Isabel Tovar, Virginea De Araujo Farias, Pedro Hernández-Cortés, Esperanza Ramirez-Moreno, Mercedes Caba-Molina, Justin Davis, Alejandro Carrero Castaño, Jose Mariano Ruiz de Almodovar, Pablo Galindo-Moreno,
Pathobiology.2024; 91(2): 132. CrossRef
circRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma
Yuenan Liu, Kailei Chen, Yi Shou, Sen Li, Jun Wang, Qingyang Zhang, Ziwei Huang, Jiaju Xu, Mingfeng Li, Di Liu, Huageng Liang, Hongmei Yang, Xiaoping Zhang
Clinical and Translational Medicine.2023;[Epub] CrossRef
Prognostic value of insulin‑like growth factor 2 mRNA‑binding protein 3 and vascular endothelial growth factor‑A in patients with primary non‑small‑cell lung cancer
Jiannan Liu, Ying Liu, Wenjing Gong, Xiangshuo Kong, Congcong Wang, Shuhua Wang, Aina Liu
Oncology Letters.2019;[Epub] CrossRef
Epithelial‑mesenchymal transition in colorectal carcinoma cells is mediated by DEK/IMP3
Shuping You, Yun Guan, Weihong Li
Molecular Medicine Reports.2017;[Epub] CrossRef

Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia: Tae Eun Kim, Hwal Woong Kim, Kyung Eun Lee; Korean J Pathol. 2014;48(1):24-29. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.24

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Abstract PDF

Background

This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections.

Methods

A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry.

Results

HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively.

Conclusions

This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes.

Citations

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Screening for High-Risk Human Papillomavirus Reveals HPV52 and HPV58 among Pediatric and Adult Patient Saliva Samples
Hunter Hinton, Lorena Herrera, Sofia Valenzuela, Katherine M. Howard, Karl Kingsley
Dentistry Journal.2024; 12(3): 56. CrossRef
Usefulness Analysis of Urine Samples for Early Screening of Human Papilloma Virus Infection
Yoon Sung Choi, Hyunwoo Jin, Kyung Eun Lee
Journal of Cancer Prevention.2019; 24(4): 240. CrossRef
Relationship between Expression of P16 and Ki-67 and Persistent Infection of HPV in Cervical Carcinoma Patients
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Advances in Clinical Medicine.2018; 08(08): 776. CrossRef
Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea
Youn Jin Choi, Eun Young Ki, Chuqing Zhang, Wendy C. S. Ho, Sung-Jong Lee, Min Jin Jeong, Paul K. S. Chan, Jong Sup Park, Xuefeng Liu
PLOS ONE.2016; 11(12): e0168178. CrossRef

Immunohistochemical Classification of Primary and Secondary Glioblastomas: Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park; Korean J Pathol. 2013;47(6):541-548. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.541

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Abstract PDF

Background

Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification.

Methods

We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases.

Results

According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs.

Conclusions

We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

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Jiamin Li, Zhihong Lan, Xiao Zhang, Xiaoyun Liang, Hanwei Chen, Xiangrong Yu
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Hiba Thankayathil, Aparna Govindan, Supriya Nilambur Kovilakam, Rajeev Mandaka Parambil
Indian Journal of Neurosurgery.2025; 14(S 01): S48. CrossRef
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Mukesh Barange, Sridhar Epari, Mamta Gurav, Omshree Shetty, Ayushi Sahay, Prakash Shetty, Jayantsastri Goda, Aliasagar Moyiadi, Tejpal Gupta, Rakesh Jalali
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Michael Nweke, Gabriel Ogun, Amos Adeleye, Clement A. Okolo, Adekunle Adesina
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Azza Abdel-Aziz, Mie A. Mohamed, Dina Abdallah, Fatma M.F. Akl, Ghada E. Eladawy, Ahmed N. Taha, Hossam Shata
Egyptian Journal of Pathology.2018; 38(1): 27. CrossRef
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John Bianco, Chiara Bastiancich, Aleksander Jankovski, Anne des Rieux, Véronique Préat, Fabienne Danhier
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Sameera Karnam, Radhika Kottu, Amit Kumar Chowhan, Prasad Chandramouleswara Bodepati
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Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis: Miji Lee, Sung Bae Kim, Sang-wook Lee, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho; Korean J Pathol. 2013;47(2):148-157. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.148

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Abstract PDF

Background

Human papillomavirus (HPV)-related tonsillar squamous cell carcinoma (TSCC) has recently been characterized as a distinct subset with a favorable prognosis. The prevalence and clinicopathologic significance of HPV-related TSCC in Koreans are not well known.

Methods

HPV in situ hybridization (ISH) accompanied by p53, p16, pRb, and cyclin D1 immunohistochemical staining were performed on 89 resection cases of TSCC from 2000 through 2010.

Results

HPV was detected by ISH in 59 of 89 cases (66.3%). HPV-positive TSCCs were more common in younger ages (p=0.005), and tumor sizes were smaller in the HPV-positive compared to the HPV-negative group (p=0.040). Positive HPV staining was significantly correlated with p16 expression (p<0.001), pRb inactivation (p=0.003), and cyclin D1 down-regulation (p<0.001) but not with p53 expression (p=0.334). Seventeen cases that showed p16-immunopositivity with HPV-negativity by ISH were retested by HPV typing; HPV DNA was not detected in all cases. There was no significant difference between HPV-positive and HPV-negative patients either in the disease-specific survival (DSS, p=0.857) or overall survival (p=0.910). Furthermore, pRb-inactivated cases showed better DSS (p=0.023), and p53-positive cases showed worse DSS (p=0.001).

Conclusions

Although high HPV prevalence was noted, it was not correlated with histopathologic findings or survival benefit. In addition to p53 expression, pRb inactivation along with p16 overexpression and down-regulation of cyclin D1 are thought to be important pathogenetic steps for developing TSCCs.

Citations

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Assessment of the Mutation Profile of Tonsillar Squamous Cell Carcinomas Using Targeted Next-Generation Sequencing
Ha Young Park, Joong Seob Lee, Jee Hye Wee, Jeong Wook Kang, Eun Soo Kim, Taeryool Koo, Hee Sung Hwang, Hyo Jung Kim, Ho Suk Kang, Hyun Lim, Nan Young Kim, Eun Sook Nam, Seong Jin Cho, Mi Jung Kwon
Biomedicines.2023; 11(3): 851. CrossRef
Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea
Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho
Journal of Pathology and Translational Medicine.2023; 57(3): 166. CrossRef
Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus–Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System
Hyunchul Kim, Mi Jung Kwon, Bumjung Park, Hyo Geun Choi, Eun Sook Nam, Seong Jin Cho, Kyueng-Whan Min, Eun Soo Kim, Hee Sung Hwang, Mineui Hong, Taeryool Koo, Hyo Jung Kim
Indian Journal of Surgical Oncology.2021; 12(S1): 134. CrossRef
Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas
Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
Journal of Pathology and Translational Medicine.2020; 54(5): 411. CrossRef
Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus–negative tonsillar squamous cell carcinoma and their prognostic significances
Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
Human Pathology.2014; 45(7): 1327. CrossRef

Expression of CHOP in Squamous Tumor of the Uterine Cervix: Hyun Hee Chu, Jun Sang Bae, Kyoung Min Kim, Ho Sung Park, Dong Hyu Cho, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung; Korean J Pathol. 2012;46(5):463-469. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.463

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Abstract PDF

Background

High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53.

Methods

Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I).

Results

CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively).

Conclusions

Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.

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Interplay between the cellular stress pathway, stemness markers, and Helicobacter pylori infection in gastric cancer
Mehran Gholamin, Atena Mansouri, Mohammad Reza Abbaszadegan, Mohammad Ali Karimi, Hossein Barzegar, Fatemeh Fardi Golyan, Hanie Mahaki, Hamid Tanzadehpanah, Reihaneh Alsadat Mahmoudian
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Role of C-reactive protein in cervical intraepithelial neoplasia/cancer
Adriana Pedreañez, Yenddy Carrero, Renata Vargas, Juan P.Hernández Fonseca, Jesús Mosquera
Pathology - Research and Practice.2025; 276: 156274. CrossRef
Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents
Ali Ahmed Azzawri, Ibrahim Halil Yildirim, Zeynep Yegin, Abdurrahim Dusak
Nucleosides, Nucleotides & Nucleic Acids.2024; 43(5): 391. CrossRef
Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology
Elif Guzel, Sefa Arlier, Ozlem Guzeloglu-Kayisli, Mehmet Tabak, Tugba Ekiz, Nihan Semerci, Kellie Larsen, Frederick Schatz, Charles Lockwood, Umit Kayisli
International Journal of Molecular Sciences.2017; 18(4): 792. CrossRef
Endoplasmic reticulum stress pathway PERK‐eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF‐κB
Qiao Qiao, Chaonan Sun, Chuyang Han, Ning Han, Miao Zhang, Guang Li
Cancer Science.2017; 108(7): 1421. CrossRef
Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells
Boyun Kim, Hee Seung Kim, Eun-Ji Jung, Jung Yun Lee, Benjamin K. Tsang, Jeong Mook Lim, Yong Sang Song
Molecular Carcinogenesis.2016; 55(5): 918. CrossRef
Down-regulation of C/EBP homologous protein (CHOP) expression in gastric cardia adenocarcinoma: Their relationship with clinicopathological parameters and prognostic significance
Xiao-Juan Zhu, She-Gan Gao, San-Qiang Li, Zhen-Guo Shi, Zhi-Kun Ma, Shan-Shan Zhu, Xiao-Shan Feng
Clinics and Research in Hepatology and Gastroenterology.2015; 39(3): 391. CrossRef
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Alteration of Apoptosis-Related Proteins (Apaf-1, Caspase-9, Bcl-2, p53, and Survivin) According to Malignant Progression in Cutaneous Melanocytic Lesions.: Yeo Ju Kang, Ji Han Jung, Kwnag Il Yim, Kyo Young Lee, Youn Soo Lee, Seok Jin Kang, Chang Suk Kang, Si Yong Kim; Korean J Pathol. 2011;45(3):247-253.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.247

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Abstract PDF: BACKGROUND
Apoptosis protease activating factor-1 (Apaf-1), caspase-9, Bcl-2, p53, and survivin are important factors in the pathway of apoptosis, but their clinicopathologic significance remains unclear in human cutaneous melanoma. We investigated the expression of these proteins and their clinical value in human cutaneous melanocytic lesions.
METHODS
We performed an immunohistochemical analysis to examine the expression and distribution of Apaf-1, caspase-9, Bcl-2, p53, and survivin in 36 cases of malignant melanoma (22 cases of primary melanoma and 14 cases of metastatic melanoma) and 41 cases of melanocytic nevus.
RESULTS
The expression of p53 was significantly higher in malignant melanoma than in melanocytic nevus (p<0.01), however the expressions of Apaf-1 and caspase-9 were significantly lower in malignant melanoma compared with melanocytic nevus (p<0.01 and p=0.027, respectively). Also, there was a significant difference for Bcl-2 staining between primary melanomas and metastatic lesions (p=0.004). Nuclear staining for survivin were absent in nevus, but were positive in 14 of 36 melanomas (p<0.01).
CONCLUSIONS
The altered expression of Apaf-1, caspase-9, p53, and survivin are considered to be related to malignant progression in human cutaneous melanocytic lesions. Loss of Bcl-2 can be considered as a prognostic marker of malignant melanomas.

Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression.: Nari Shin, Hye Yeon Kim, Woo Kyung Kim, Min Gyung Park, Kyung Bin Kim, Dong Hoon Shin, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Gi Young Huh, Mee Young Sol, Do Youn Park; Korean J Pathol. 2011;45(1):69-78.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.69

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Abstract PDF

BACKGROUND
It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer.
METHODS
We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH).
RESULTS
Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes.
CONCLUSIONS
Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type.

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Mucin Expression in Gastric Cancer: Reappraisal of Its Clinicopathologic and Prognostic Significance
Dae Hwan Kim, Nari Shin, Gwang Ha Kim, Geum Am Song, Tae-Yong Jeon, Dong-Heon Kim, Gregory Y. Lauwers, Do Youn Park
Archives of Pathology & Laboratory Medicine.2013; 137(8): 1047. CrossRef
Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes
Joo-Yeun Kim, Na Ri Shin, Ahrong Kim, Hyun-Jeong Lee, Won-young Park, Jee-Yeon Kim, Chang-Hun Lee, Gi-Young Huh, Do Youn Park
Korean Journal of Pathology.2013; 47(1): 28. CrossRef

Uncoupling Protein 2 (UCP2) and p53 Expression in Invasive Ductal Carcinoma of Breast.: Kyu Yeoun Won, Gou Young Kim, Youn Wha Kim, Sung Jig Lim, Jeong Yoon Song; Korean J Pathol. 2010;44(6):565-570.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.565

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Abstract PDF

BACKGROUND
Uncoupling protein 2 (UCP2) is a recently identified mitochondrial inner membrane anion carrier and a negative regulator of reactive oxygen species production. In this study, we evaluated the characteristics and relationships of UCP2 and p53 expression in breast cancer tissues.
METHODS
Tissue microarray slides from 107 cases of invasive ductal carcinoma of the breast were constructed, UCP2 and p53 immunohistochemical staining was conducted, and clinicopathological correlations were investigated.
RESULTS
UCP2 expression in invasive ductal carcinoma was high in 53 cases (49.5%), while p53 expression in invasive ductal carcinoma was high in 37 cases (34.6%). UCP2 expression was correlated significantly with histological grade (p = 0.038) and mitotic count (p = 0.050). UCP2 expression was correlated significantly with p53 expression in invasive ductal carcinoma of the breast (p = 0.045). UCP2 expression (p = 0.8308) and p53 expression (p = 0.3292) showed no significant difference for the overall survival rate in patients with invasive ductal carcinoma.
CONCLUSIONS
UCP2 expression in invasive ductal carcinoma increased proportionally with histological grade and mitotic count. High UCP2 expression in invasive ductal carcinoma was observed in conjunction with high p53 expression.

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Forkhead box protein A1 inhibits the expression of uncoupling protein 2 in hydrogen peroxide-induced A549 cell line
Lan Song, Zhaojun Xu, Ling Li, Mei Hu, Lijuan Cheng, Lingli Chen, Bo Zhang
Cell Stress and Chaperones.2014; 19(1): 53. CrossRef
New Aspects of Mitochondrial Uncoupling Proteins (UCPs) and Their Roles in Tumorigenesis
Delira Robbins, Yunfeng Zhao
International Journal of Molecular Sciences.2011; 12(8): 5285. CrossRef

The Expressions of E2F1 and p53 in Gastrointestinal Stromal Tumors and Their Prognostic Significance.: Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jong Seok Lee, Chan Heun Park, Woon Geon Shin; Korean J Pathol. 2009;43(3):212-220.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.212

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Abstract PDF

BACKGROUND
E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors.
METHODS
Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate.
RESULTS
1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008).
CONCLUSIONS
E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.

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Comparison of tissue microarray and full section in immunohistochemistry of gastrointestinal stromal tumors
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jun Ho Park, Chan Heun Park, Won Jae Lee
Pathology International.2009; 59(12): 851. CrossRef

The p53 Mutation and DNA Ploidy in Human Metastatic Breast Cancer.: Seong Jin Cho, Ae Ree Kim, Nam Hee Won; Korean J Pathol. 1997;31(2):135-144.

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Abstract PDF: The p53 gene, one of the tumor suppressor genes, is believed to play an important role through mutation and overexpression in the progression of various human malignant tumors. To compare the p53 mutation status between the primary and metastatic lesions of breast cancers and to investigate the mutational pattern of p53, immunohistochemistry (IHC) and polymerase chain reaction and single strand conformational polymorphism (PCR-SSCP) were performed in 25 cases of breast cancers with paraffin embedded tissue. Mutant protein products or point mutation were detected through IHC or PCR-SSCP method. And flow cytometrical (FCM) analysis were performed in the same paraffin blocks to correlate the DNA ploidy and p53 mutation. The following results are summarized. 1. The detection of the p53 gene mutation and overexpression of the p53 protein were measured in 40% and 48%, respectively, in 25 primary tumors, either or both methods was detected in 64%. 2. A concordance rate of the p53 protein expression between the primary and metastatic lesions of 25 breast cancers was 100%, but the concordance rate of the p53 gene mutation was 72%. 3. The correlation between the p53 mutation and the DNA aneuploidy was not statistically significant (p=0.38) 4. A p53 mutation by IHC or PCR-SSCP was more frequently detected in grade III breast cancers than in grade I or II. 5. Among 5 to 9 exons of the p53 gene, exon 7 was the most frequent mutation spot in this study. 6. Additional mutation of the p53 gene was developed in the three metastatic lesions. With the above results it is suggested that the p53 protein overexpression by immunohistochemistry is not correlated with the p53 mutation by PCR-SSCP. The p53 mutation pattern between the primary and metastatic lesions are not idenitical and an additional point mutation can occur in the metastatic lesion. The DNA aneuploidy is more frequently detected in the cases with the p53 protein overexpression than in the p53 protein negative, but it is not statistically significant.

Expressions of MIB-1, p53 and CEA in Endocervical Glandular Lesions.: Mi Jin Kim, Young Gi Lee, Dong Sug Kim; Korean J Pathol. 2001;35(1):41-47.

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Abstract PDF: BACKGROUND
Endocervical glandular lesions include glandular atypia (GA), endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS), and invasive adenocarcinoma (IA). The diagnosis of malignant glandular lesions is occasionally difficult to distinguish from benign mimickers, and the morphologic features of EGD remain unsettled.
METHODS
Immunohistochemical stains for MIB-1, p53 and CEA were performed on 81 cases of paraffin-embedded endocervical glandular lesions including 22 IA, 15 AIS, 15 EGD, 13 GA, 8 microglandular hyperplasia (MGH) and 8 tubal metaplasia (TM).
RESULTS
The MIB-1 labelling index of IA was 59.68%, 69.53% for AIS, 26.60% for EGD, 16.03% for benign. p53 overexpression was noted in 4 (18%) cases of IA, 3 (20%) of AIS, but none of EGD and benign lesions. It was Interesting to note that one case of MGH showed p53 staining in low intensity. Diffuse strong cytoplasmic CEA positivity was present in all of IA and AIS, whereas seven (47%) of 15 EGD and 12 (41%) of 29 benign lesions showed focal cytoplasmic CEA positivity. There were significant differences in MIB-1 and CEA immunostainings among the adenocarcinoma, EGD, and benign glandular lesions. Adenocarcinoma was closely related to p53 overexpression, although occurring in a low percentage of the cases.
CONCLUSION
MIB-1 immunostaining can be useful in differentiating among endocervical adenocarcinoma, endocervical glandular dysplasia and benign glandular lesions. p53 overexpression might be helpful in the diagnosis of adenocarcinoma.

Telomerase mRNA Expression by In Situ Hybridization in Premalignant Lesions and Carcinomas of the Breast.: Young Kyung Bae, Dong Sug Kim, Soo Jung Lee, Koing Bo Kwun; Korean J Pathol. 2001;35(1):53-59.

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Abstract PDF: BACKGROUND
Telomerase is a ribonucleoprotein, DNA polymerase that synthesizes telomere repeats onto chromosomal ends and maintains telomere length. Telomerase activity has been detected in a broad range of human malignant neoplasms, but not in normal somatic cells. So, activation of telomerase may represent an essential step in the malignant transformation of cells. However, the expression of telomerase in premalignant lesions remains relatively unexplored. This study was conducted to investigate the reactivation of telomerase in the carcinogenesis of human breast tissue.
METHODS
In situ hybridization for the telomerase RNA component (human telomerase mRNA; hTR) was used in a normal breast tissue (n=41), florid ductal hyperplasia (FDH) (n=10), atypical ductal hyperplasia (ADH) (n=3), ductal carcinoma in situ (DCIS) (n=44) and invasive carcinoma (n=33). hTR expression in relation to p53 status and the pathologic parameters in breast cancer was also studied.
RESULTS
Expression of hTR was demonstrated in 13 samples (31.7%) of normal breast tissues, 4 (40%) of FDH, 3 (100%) of ADH, 42 (95.5%) of DCIS, and 33 (100%) of invasive carcinoma. The rate of hTR expression of ADH was significantly different from that of FDH (p<0.05), and there were no differences in hTR expression rates among ADH, DCIS and invasive carcinomas. There was no correlation between hTR expression and nuclear grade, tumor size, and p53 status in invasive carcinomas.
CONCLUSION
These results suggest that telomerase activation may be an early event and an essential step in the carcinogenesis of human breast tissue, and that telomerase has no correlations with p53 status and prognostic parameters.

Expression of c-fos, p53, Transforming Growth Factor-beta1 and Glial Fibrillary Acidic Protein in Hippocampus Following Transient Forebrain Ischemia in Mongolian Gerbil.: Jae Hwa Lee, Bang Hur; Korean J Pathol. 2001;35(1):60-70.

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Abstract PDF: BACKGROUND
Recent studies have shown that delayed neuronal death is closely associated with early gene (c-fos or c-jun)-related apoptosis in addition to hypoxia-induced energy deficiency in the hippocampus.
METHODS
To elucidate the role of c-fos, p53, TGF-1 and glial fibrillary acidic protein (GFAP) and their interactions, cellular expression with immunohistochemistry was examined during the time period of 10-minute hypoxia with variable reperfusion intervals in the mongolian gerbil hippocampus.
RESULTS
Hippocampal CA1 shows progressive and delayed neuronal damage beginning from the 24-hour reperfusion, while CA2-3 reveals non-progressive, eosinophilic inclusion body within the neuron throughout the time period. CA1 neurons show short-term expressions of c-fos prior to significant cellular damage. However, CA2-3 neurons show persistent expressions by 3-day reperfusion. In both CA1 and CA2-3, p53 is expressed for the short-term period of the early time points. However, its intensity and duration are much less in CA2-3 than in CA1. While TGF-1 is transiently expressed at 24-hour reperfusion in CA1, its expression in CA2-3 is persistent in late time points. Early expression of GFAP is observed in the pyramidal layer of CA1 prior to neuronal damage and progressively increased in the late time points.
CONCLUSION
These results suggest that c-fos and TGF-1 may play a role in neuronal viability in the early- and late time points. Astrocytes may also be responsible for the active protective mechanism to neuronal death, as well as reactive gliosis. The hypoxia-induced neuronal damage is, in part, a p53-dependent process in the CA1 neurons.

Expression of E-cadherin and p53 Proteins in Gastric Adenocarcinoma.: Sook Hee Hong, Mee Sook Roh; Korean J Pathol. 1999;33(2):80-87.

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Abstract: The gastric carcinoma shows various molecular and genetic alterations in its development and progression. There are evidences that the changes of the expression of cell adhesion molecules affect the morphogenesis of the tumor as well as the tumor progression and metastasis. The purpose of this study is the evaluation of the expression pattern of a cell adhesion molecule, E-cadherin, and a tumor suppression gene, p53, by immunohistochemical stain and the relationship of their expressions with clinicopathologic findings in gastric adenocarcinoma tissue. The E-cadherin expression was absent or reduced in 93 cases (73.2%) and p53 was positive in 98 cases (77.2%) of 127 gastric adenocarcinomas. The frequency of reduced E-cadherin expression was significantly higher in poorly differentiated adenocarcinomas (p=0.04) and in diffuse type (p=0.01), but that of p53 positivity was not significantly correlated with tumor differentiation. Both proteins showed no correlation with depth of invasion, lymph node and distant metastasis, and tumor stage. There was no correlation between E-cadherin and p53 expression. This study indicates that the altered expressions of E-cadherin and p53 are associated with the development of intestinal and diffuse types of gastric adenocarcinoma and the differentiation of the gastric adenocarcinoma is affected by cell adhesion mediated by E-cadherin, but the modes of tumor progression and metastasis are not affected by E-cadherin and p53.

The Expression of p53, c-erbB-2 and nm23 Proteins in Breast Cancer.: Kyo Young Lee, Yong Goo Kim, Young Shin Kim, Kyung Ja Han, Chang Suk Kang, Jean A Kim, Won Il Kim, Sang In Shim; Korean J Pathol. 1999;33(2):88-95.

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Abstract: Recently, p53, c-erbB-2 and nm23 proteins have been studied in breast cancer. The expression of p53 protein indicates the mutation of p53 gene known as a tumor supressor gene, and c-erbB-2 gene amplification has been considered an indicator of poor prognosis and nm23 a metastsis suppressor gene. In order to elucidate the roles and relations of these proteins in the develpoment, progression and metastasis in breast cancer, we studied 89 cases of invasive breast cancer and 32 cases of lymph node metastasis for the expression of p53, c-erbB-2 and nm23 proteins using an immunohistochemical method. The results were as follows: 1) The expression rates of p53, c-erbB-2, and nm23 proteins in breast cancer were 40.4%, 34.8% and 55.1%, respectively. Co-expression of p53 protein and c-erbB-2 protein was found in 20.2% of cases, showing the highest incidence in poorly differentiated type (40%). 2) p53 protein expression was increased in poorly differentiated type but was not statistically significant. On the other hand, the expression of nm23 protein was decreased in poorly differentiated type, which was statistically significant (p<0.05). 3) The correlation of p53 protein expression with c-erbB-2 protein expression was statistically significant (p<0.05) but that with nm23 protein was not. 4) In the cases with lymph node metastasis, discordant expression of p53, c-erbB-2 and nm23 proteins between primary tumor and the lymph node metastatic tumor was found in 9.4%, 3.1% and 18.8% of cases, respectively. The above results suggest that overexpression of p53 and c-erbB-2 proteins and downregulation of nm23 protein are associated with the tumor progression in the breast cancer.

Loss of Heterozygosity Affecting the APC and p53 Tumor Suppressor Gene Loci in Colorectal Cancers and Its Prognostic Significance.: Eun Deok Chang, Won Sang Park, Byung Kee Kim, Sun Moo Kim, Sang In Shim; Korean J Pathol. 1997;31(3):191-200.

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Abstract PDF: Development of the human colorectal cancer is associated with several distinct genetic abnormalities involving both dominant-acting oncogenes (K-ras, c-src) and tumor suppressor genes (APC, DCC, p53) which undergo inactivation or loss. In colorectal tumors, the common molecular alteration is localized in the 17p13 and 5q21 loci encoding the p53 and the APC gene, respectively. The identification of these genes may help the understanding of the pathogenesis of colorectal neoplasia. In order to determine whether the frequency of the genetic alterations varies with sex, age, tumor size, or site, including pathologic parameters, such as degree of differentiation, tumor stage, mucin component, lymphoid reaction, tumor invasion pattern, vein and nerve invasion, lymph node metastasis, and other parameters, such as disease-free survival, distant metastasis and patient outcome, the authors analyzed the loss of heterozygosity (LOH) of the APC and the p53 genes in paraffin-embedded specimens of 48 colorectal cancers by use of the polymerase chain reaction and restriction fragment length polymorphism. The results were as follows: the LOH affecting the APC was found in 15 out of 31 (48.4%) heterozygous patients, while the LOH of the p53 locus was observed in 11 out of 26 (42.3%) patients. Among 48 patients, the LOH at both the APC and the p53 loci was observed in five (10.4%) patient. No statistically significant associations were found between the LOH of the APC gene and the proposed parameters. The relationship between the LOH of the p53 and the histologic differentiation, lymphoid reaction was significant (P<0.05), but survival was not correlated. Statistically significant associations were found between overall survival of the colorectal cancer patients and distant metastasis, Astler-Coller stage, lymphoid reaction, invasion pattern, nerve invasion, vein invasion, lymph node metastasis, and disease free survival. The above results suggest that the LOH of the p53 genes could be involved in the progression of colorectal cancers. However, neither the LOH of the APC nor that of the p53 have significant association with survival of the colorectal cancer patients.

Heat Shock Protein 70 and p53 Protein Expression in Colorectal Adenomas and Carcinomas.: Tae Jung Jang, Jung Ran Kim, Kung Bae Lee; Korean J Pathol. 1997;31(3):201-210.

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Abstract PDF: Heat shock protein 70 (HSP70) is a chaperone that binds to mutant p53 and consequently can regulate its accumulation or localization. Its expression is upregulated in tumor cells. We studied 44 adenomas and 29 carcinomas of colorectum to evaluate the expression of HSP70, and to assess the correlation among p53 protein and other clinical prognostic parameters. HSP70 expression was scored according to staining intensity and extent. p53 protein expression was 45.5%(20/44) in adenomas and 79.3%(23/29) in carcinomas(P<0.01). p53 protein expression of carcinomas was 57.1%(4/7) in diploidy tumors, 100.0%(8/8) in aneuploidy tumors(P=0.07), 100.0%(8/8) in well-differentiated tumors, and 50.0%(2/4) in poorly differentiated tumors(P= 0.09). HSP70 expression mainly revealed a fine granular cytoplasmic staining pattern in tumor cells. HSP70 was focally detected in some lymphocyte, ganglion cell and normal mucosa. HSP70 expression was 46.3%(19/41) in adenomas and 93.1%(27/29) in carcinomas. HSP70 score was 0.9+/-1.3 in adenomas(n=41) and 5.5+/-3.5 in carcinomas(n=29)(P<0.0005). Its score was 1.7+/-1.6 in p53 positive adenomas and 0.3+/-0.6 in p53 negative adenomas(P<0.005), and its expression rate was higher in p53 positive carcinomas than p53 negative carcinomas (P>0.05). There was no significant correlation among HSP70, tumor size, Dukes'stage, nodal metastasis, depth of tumor invasion, DNA ploidy and tumor differentiation. In conclusion, HSP70 and p53 protein appear to be correlated to each other, and that HSP70 and p53 protein may play a certain role in the progression of colorectal tumor. Further studies are needed for determining their prognostic factors in colorectal carcinoma.

Case Report

Intraductal Cystic Hypersecretory Carcinoma of the Breast: A case report.: Jin Haeng Chung, Seung Sook Lee, Jae Soo Koh, Kyung Ja Cho, Jong Inn Lee; Korean J Pathol. 1999;33(2):137-140.

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Abstract: The cystic hypersecretory duct carcinoma of the breast was first described in 1984 by Rosen and Scott and warrants separate discussion because of its unusual pathological features. It is morphologically distinguishable from juvenile (secretory) carcinoma and from mucinous (colloid) carcinoma or mucocele-like tumor. We present a case report of intraductal cystic hypersecretory carcinoma of the breast with hormone receptor and oncogene study. The histologic differential diagnosis, with an emphasis on benign lesions that may have a predominant cystic component, is also discussed.

Original Articles

A Study of the Relationship between p53 Mutation and Proliferating Activities in Astrocytic Tumors.: Geun Ho Lee, Jong Sang Choi; Korean J Pathol. 1999;33(3):158-168.

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Abstract PDF: To evaluate the relationship between p53 protein expression and proliferating activity in astrocytic tumors, we performed a study using 37 cases of astrocytic tumors; 13 cases of low-grade astrocytoma (LGA), 9 cases of anaplastic astrocytoma (ANA), and 15 cases of glioblastoma multiforme (GM). The p53 protein expression was studied by immunohistochemical staining (IHC) with DO-7 monoclonal antibody in 37 cases and p53 mutation was detected by single strand conformational polymorphism (SSCP) using PCR products of 31 cases. Proliferating activities were detected by Ki-67 (MIB-1) and proliferating cell nuclear antigen (PCNA). Immunohistochemically, 24.3% (9/37) of astrocytic neoplasms showed p53 expression, which consisted of 7.7% (1/13) of LGA, 44.4% (4/9) of ANA, and 26.7% (4/15) of GM. The p53 expression was statistically significant between the tumor grades. p53 mutations on exon 5 were noted in 6 (19.4%) out of 31 cases of astrocytic tumors. Average indices of MIB-1 and PCNA were 1.5 2.6% and 7.0 10.1% in LGA, 10.0 12.7% and 23.7 23.2% in ANA, and 30.9 22.4% and 69.9 26.7% in GM, respectively. p53 positive group by IHC showed significantly higher average MIB-1 (26.2 23.5%) and PCNA index (56.7 30.3%) than those (12.1 18.3%, 27.6 29.6%) of p53 negative group (p<0.05). p53 mutation group also showed significantly higher MIB-1 (30.7 26.0%) and PCNA index (55.5 32.6%) than those without p53 mutation (10.8 16.5%, 24.2 28.7% respectively). These results showed that about one-fifth of astrocytic tumors have p53 abnormalities, which were related with higher proliferating activities than those without p53 abnormalities.

bcl-2 and p53 Protein Expression in Multiple Myeloma and Non-tumorous Plasma Cells A study related to survival.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Young Jae Lee; Korean J Pathol. 1999;33(3):179-186.

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Abstract PDF: The gene product of bcl-2 (B-cell leukemia/lymphoma-2) was suggested to suppress programmed cell death (apoptosis) of tumor cells and be involved in the development of multiple myeloma. However, the normal plasma cells also express the protein. It is unclear whether the expression of bcl-2 in multiple myeloma is of normal character or of regulatory adaptation in association with neoplastic transformation. p53 was also suggested to be involved in tumor progression since mutations on p53 were found in multiple myeloma. In order to find the relationship between the expression patterns of bcl-2 and p53 in tumor cells of multiple myeloma and non-neoplastic plasma cells, we examined 38 cases of multiple myeloma and 10 cases of nasal polyp immunohistochemically. Furthermore, expression of bcl-2 and p53, mitosis, clinical stage and infiltrative pattern of tumor cells in bone marrow were also evaluated in association with the survival of patients. By immunostaining with anti-bcl-2 and p53 monoclonal antibody, 37 out of 38 cases of multiple myeloma and all of 10 cases of nasal polyp were positive for bcl-2 but only 7 cases of multiple myeloma were positive for p53. Marked dysplasia, low percentage of bcl-2 expression, and increased mitoses were correlated with poor prognosis. Based on these observations, we suggest that bcl-2 and p53 are involved in tumorigenesis of multiple myeloma and the survival of patients would be influenced by dysplastic change, mitosis and degree of bcl-2 expression.

Ethnic Differences of the p53 Genetic Alteration in Cutaneous Malignant Melanoma.: Won Sang Park, Eun Young Na, Sang Kyu Lee, Sug Hyung Lee, Su Young Kim, Seok Jin Kang, Kye Yong Song, Suk Woo Nam, Nam Jin Yoo, Jung Young Lee; Korean J Pathol. 2001;35(2):158-164.

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Abstract PDF: BACKGROUND
There are significant differences in the clincopathologic pattern including the incidence, favor site, and histopathologic type between cutaneous malignant melanomas arising from whites, asians and blacks. These differences might suggest that there is a racial difference in the molecular tumorigenesis mechanism of malignant melanoma.
METHODS
To determine the ethnic differences in tumorigenesis of malignant melanoma, we performed loss of heterozygosity (LOH) and sequencing analyses of the p53 gene in cutaneous malignant melanomas arising from 22 white American, 30 Korean and 15 black African patients.
RESULTS
The frequency of LOH of the p53 gene is only 12.5% in white American patients, but the frequency is significantly higher in Korean (42.1%) and black African (61.5%) patients. We also detected 17 mutations (nonsense: 1, missense: 16) of the p53 gene in the cutaneous malignant melanomas of Koreans and black Africans, but none in those of white Americans: among the 16 missense mutations, 10 mutations were C:G to T:A transitional mutations. Of these, we also detected one GG (CC) to AA (TT) tandem mutation at the pyrimidine sequence.
CONCLUSION
These results strongly suggest that there might be a racial difference in molecular carcinogenesis mechanisms among the cutaneous malignant melanomas occurring in white American, Korean and black African patients. But the role of the p53 genetic alteration in the genesis of melanomas in Korean and black African patients is subject to further evaluation.

Expression of p21 and p53 Proteins in Gastric Adenocarcinoma.: Yun Jung Kim, Young Hee Choi, Kyoung Chan Choi, Young Euy Park; Korean J Pathol. 1999;33(3):187-192.

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Abstract PDF: Fifty-four adenocarcinomas of stomach were investigated to assess the expression of p21 and p53 using an immunohistochemical method. The relationship between p21 and p53 expression and the clinicopathologic parameters were analysed. The staining pattern of p21/p53 were: p21+/p53+, p21-/p53+, p21+/p53-, and p21-/p53- in 30, 12, 8, and 4 cases, respectively. Loss of p21 expression was observed in 16 of 54 tumor tissues (29%). p21 expression, however, had an inverse correlation with vascular invasion and depth of tumor invasion. The p21 and p53 protein expression showed intratumoral heterogeneity. In 63% of the adenocarcinoma, a proportional relationship was found between p21 and p53 immunostaining. The present results suggest that p53 independent induction of p21 expression may be involved in the molecular mechanism of these tumors, and expression of p21 protein may be related to a favorable prognosis in gastric adenocarcinomas.

The Expression of c-erbB-2, EGFR, p53 and Ki-67 in Ovarian Borderline Tumors and Carcinomas of the Ovary.: Kyueng Whan Min, Moon Hyang Park; Korean J Pathol. 2007;41(5):296-306.

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Abstract PDF: BACKGROUND
An ovarian surface epithelial tumor is a heterogenous disease, and various biological and molecular factors are important for its development and progression. Several findings support EGFR or c-erbB-2 as adverse prognostic indicators for an ovarian carcinoma.
METHODS
We reviewed the histological and clinical findings of 52 carcinomas (17 endometrioid, 16 serous, 13 mucinous and 6 clear cell tumors), and 26 borderline (10 serous and 16 mucinous) tumors. Expression of c-erbB-2, EGFR, p53, and Ki-67 was evaluated on paraffinembedded tissue from a primary ovarian tumor by immunohistochemical methods.
RESULTS
Expression of c-erbB-2 was found in 7.6% of tumors and expression of EGFR was found in 9.6% of tumors by immunohistochemical analysis. No significance was found between cerbB- 2 and EGFR expression as indicators of a poor prognosis. The expression of p53 and Ki-67 (>50%) correlated with the grade and type of tumor in the ovarian cancers. p53 and Ki- 67 overexpression (>50%) was absent in the borderline ovarian tumors, whereas ovarian carcinomas showed expression of both p53 and Ki-67.
CONCLUSION
Expression of c-erbB- 2, EGFR, p53, and Ki-67 as determined by immunohistochemical analysis did not correlate with prognostic significance. However, p53 and Ki-67 expression may be used as markers to predict aggressive behavior, and to differentiate between malignant and borderline epithelial ovarian tumors. Further large-scale studies are required to clarify the significance of c-erbB-2 and EGFR expression in ovarian tumors.

Genetic Expression Pattern of Gastric Carcinomas According to Cellular Mucin Phenotypes.: Won Ae Lee, In Soo Suh, Ying Hua Li, Ji Hyun Eum, Wan Sik Yu, Han Ik Bae; Korean J Pathol. 2007;41(5):307-315.

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Abstract PDF: BACKGROUND
Gastric carcinomas (GCs) have recently been reclassified according to the mucin phenotypes. We aimed to characterize the relationship between the mucin phenotypes and the genetic alterations or the clinicopathologic parameters of GCs.
METHODS
Immunohistochemistry was performed for MUC1, MUC5AC, MUC6, MUC2, CD10, p53, hMLH1, CerbB2 and E-cadherin in 150 GCs. The mucin phenotypes of the GCs were classified as 4 phenotypes: gastric, intestinal, mixed and unclassified.
RESULTS
MUC1, MUC5AC, MUC6, MUC2 and CD10 were expressed in 63.3%, 42.7%, 14.0%, 24.7% and 14.0% of the GCs, respectively. The mucin phenotypes of the GCs corresponded to the gastric type in 31.3%, the intestinal type in 20.0%, the mixed type in 15.3% and the unclassified type in 33.3%. The incidence of a p53 overexpression was higher in the gastric or mixed phenotype than in the intestinal or unclassified phenotype. MUC5AC expression, p53 overexpression and the gastric or mixed phenotype were associated with poor patient survival by multivariate analysis.
CONCLUSION
This study suggests the gastric or mixed mucin phenotype may more likely go through the p53 pathway in carcinogenesis and the mucin phenotype may be considered as a prognostic indicator.

The Significance of the Expression of p53, E-cadherin, nm23, CD44, and Tumor Angiogenesis in Colorectal Adenocarcinoma.: Sung Suk Paeng, Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(4):314-325.

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Abstract PDF: Many oncogenes and tumor supressor genes have been identified and studied in colorectal carcinoma. Among them, p53 is a tumor supressor gene and its mutation is frequently noted in human tumors. E-cadherin is a cell adhesion molecule and associated with tumor differentiation. CD44 is a cell surface glycoprotein that plays a role in cell migration and metastasis. nm23 is a gene known to lower metastatic potential of tumors and has been proposed to be a metastasis supressor gene. Tumor angiogenesis is required for the expansion of the primary tumor and metastasis and its degree is related to the potential of malignancy. We studied the expression of p53, E-cadherin, nm23, CD44 and tumor angiogenesis in 36 cases of colorectal adenocarcinomas. They were compared with previously known prognostic factors such as the stage, tumor size, depth of invasion, differentiation, presence of lymphatic or venous invasion, the lymph node and distant metastasis. The results were as follows. 1) The expression of p53 was not significantly associated with any prognostic factors. 2) The expression of E-cadherin was significantly associated with tumor differentiation. In the well differentiated adenocarcinomas, its expression was higher than in the poorly differentiated adenocarcinoma. 3) The expression of nm23 was also significantly associated with tumor differentiation. In carcinoma with lymph node metastasis, the expression of nm23 was reduced, but statistically it was not significant. 4) The expression of CD44 was higher in tumors with lymph node metastasis than in tumors without lymph node metastasis, but it was not statistically significant. 5) The degree of microvessel density was significantly associated with lymphatic invasion. According to the above results, the expression of E-cadherin and nm23 are related to the differentiation of the tumor and tumor angiogenesis is related to the lymphatic invasion of the colorectal adenocarcinoma.

The Prognostic Significance of p53 Protein and PCNA in Advanced Gastric Carcinoma.: Ho Won Hwang, Hyung Bae Moon; Korean J Pathol. 1995;29(4):450-458.

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Abstract PDF: The 5 year-survival rates were examined to evaluate the prognositic significance of the expression of the p53 protein and the positivity of the PCNA in 108 cases of advanced gastric carcinoma. The p53 protein and PCNA were stained by immunohistochemistry in the tissue of the gastrectomized specimen. The results were as follows. 1) The overall 5 year-survival rate of advanced gastric carcinoma was 42.3 % and the significant prognostic factors were a pathologic stage and p53 protein(p<0.005). 2) The expanding or infiltrating type by Ming's classification and the intestinal or difftise type by Lauren's classification had similar prognosis. 514_ @@l %R-t 3) The 5 year-survival rate of the p53-positive group was 25.1% and that of p53-negative group was 56.1%(p<0.005). 4) The 5 year-survival rate of the PCNA low-grade tumors by PCNA stain(<50%)was 48.7% and that of the high-grade tumor(>=50%)was 29.9%(p>0.1). 5) There was a tendency to have a good prognosis in the p53-negative group and low grade tumors in the stage 11, III, and IV. There was a significant difference between p53 protein positive and negative groups in the stage III(p<0.005), but no significant differences were found in the other groups. The above results indicate that the p53 protein is an another useful tool for prediction of the prognosis in advanced gastric carcinoma.

Significance of Cyclin E, p53, E-cadherin, and beta-Catenin Expressions in Gastric Adenocarcinomas.: Long Pei Xuan, Mi Ja Lee, Chae Hong Suh; Korean J Pathol. 2004;38(4):213-220.

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Abstract PDF: BACKGROUND
Gastric cancer is reported to be one of the leading causes of mortality in Korea. Our aim was to evaluate the clinicopathologic usefulness of cyclin E, p53, E-cadherin and beta-catenin expressions in gastric adenocarcinomas.
METHODS
Immunohistochemical staining was performed on the 40 early gastric carcinoma (EGC) cases and 69 advanced gastric carcinoma (AGC) cases to examine the relationship with the clinicopathologic parameters.
RESULTS
Cyclin E and p53 expressions were significantly lower in the mucosal or submucosal invasion group compared with those in the muscle invasion and subserosal or serosal invasion groups. Cyclin E expression was significantly higher in the node-positive group compared with that in the node-negative group. The loss of beta-catenin expression was significantly higher in the node-negative group. p53 expression was significantly higher in the intestinal type group than that in the diffuse type group. Loss of E-cadherin expression was significantly higher in the diffuse type group. Cyclin E expression correlates with p53 expression.
CONCLUSIONS
The depth of invasion seems to correlate with cyclin E and p53 expressions. Lymph node metastasis may correlate with loss of beta-catenin expression.

Tissue Microarray Analysis of the Expression of p53, c-kit and CD34 in Sarcomas.: Jinyoung Yoo, Kyung Shin Park, Seok Jin Kang, Chang Suk Kang; Korean J Pathol. 2004;38(4):221-227.

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Abstract PDF: BACKGROUND
Our objectives in this study were to (1) evaluate the possible role of p53, c-kit and CD34 proteins in sarcomas and to determine their potential relationship; (2) use a tissue microarray to compare the immunohistochemical staining results on both the tissue microarrays and the corresponding whole tissue sections.
METHODS
Whole sections from 85 sarcomas were studied for the immunohistochemical expression of p53, c-kit and CD34. Tissue microarrays consisting of triplicate 2 mm cores from the corresponding blocks were constructed and stained according to the same protocols as those used for the whole sections.
RESULTS
On whole section analysis, p53 protein was expressed in 25 cases (29.4%). Expression of c-kit was observed in 31 specimens (36.5%), whereas CD34 expression was noted in 11 tumors (12.9%). The overall concordance between triplicates was 96% (217/226). The consensus score from the combined triplicates agreed with the results on the whole sections at 91.4% (233/255). The correlations between p53 and CD34, and between c-kit and CD34, were statistically significant (p=.028 and p=.010 respectively).
CONCLUSIONS
p53 and c-kit express relatively frequently in sarcomas. Tissue microarrays are an effective alternative to whole sections; however, the presence of triplicate punches seems to improve the yield but not the concordance of data.

Immunohistochemical Expression of p53, p21, and mdm2 Proteins in Human Papillomavirus Positive and Negative Invasive Uterine Cervical Carcinomas.: In Seo Park, Hye Seung Han, Tae Sook Kim, Jee Young Han, Joon Mee Kim, Young Chae Chu, Tae Sook Hwang; Korean J Pathol. 2001;35(3):212-219.

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Abstract PDF: BACKGROUND
In the uterine cervical carcinoma, the inactivation of p53 protein by human papillomavirus(HPV) E6 protein has been reported to play a greater role in carcinogenesis than the mutation of the p53 gene. Therefore, the mutation of the p53 gene is rare. p21 and mdm2 proteins are induced by wild-type p53 protein and are involved in the cell cycle regulatory mechanism.
METHODS
Immunohistochemical staining for p53, p21 and mdm2 proteins was performed in 26 HPV-positive and 13 HPV-negative invasive cervical carcinomas together with 5 non-neoplastic cervical tissues.
RESULTS
The frequencies of the expression of p53, p21 and mdm2 proteins were 82.1%, 84.6% and 66.7%, respectively. The expression of p53 protein was less frequently demonstrated in HPV-positive cases than HPV-negative cases, which was statistically a negative correlation(p=0.018). The expression of p53 and p21 proteins was statistically significant(p=0.000).
CONCLUSIONS
p53, p21 and mdm2 proteins were highly expressed in both HPV-positive and HPV-negative cervical carcinomas. Significantly higher expression of p53 protain in HPV-negative cases necessitate a further study for investigating the role of p53 protein accumulation in carcinogenesis of HPV-negative cervical carcinomas. The relationship between the expression of p53 protein and p21/mdm2 proteins may indicate that p21 and mdm2 proteins also have a role in carcinogenesis, where p53 protein plays a fundamental role.

Studies on the Expression of the p16 (INK4A), p53, and Ki-67 Labeling Index in Inflammatory and Neoplastic Diseases of the Uterine Cervix.: Jong Sil Lee, Jeong Gyu Shin, Gyung Hyuck Ko, Jeong Hee Lee, Hwal Woong Kim; Korean J Pathol. 2004;38(4):238-243.

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Abstract PDF: BACKGROUND
Prior studies of p16, p53, and Ki-67 expression have suggested that these markers may be preferentially expressed in cervical neoplasms. The purpose of this study was to assess the expression and clinical significance of p16, p53 proteins, and the Ki-67 labeling index in the cervical lesions.
METHODS
We analyzed 54 uterine cervical specimens obtained by surgical biopsy. The expression of p16, p53 proteins, and Ki-67 was evaluated by immunohistochemical methods. The immunohistochemical findings were then correlated with the histologic diagnosis.
RESULTS
Positive scores for p16, p53, and Ki-67 were seen in 75% (6/8), 0% (0/8), and 13% (1/8) of low grade intraepithelial lesions (LSIL), respectively, and 100% (23/23), 17% (4/23), and 74% (17/23) of high grade intraepithelial lesions (HSIL), respectively, and 100% (10/10), 20% (2/10), and 70% (7/10) of invasive squamous cell carcinomas, respectively. Both normal epithelium and inflammatory lesions scored negative for these three markers in all of the 13 cases. p16 and Ki-67 expression correlated with the severity of uterine cervix lesions.
CONCLUSIONS
p16 and Ki-67 are complementary surrogate biomarkers for cervical squamous intraepithelial neoplasia. However, immunohistochemical expression for p53 has no correlation with the grade of cervical squamous intraepithelial neoplasia.

Correlation between Expression of p53 Protein and Prognostic Factors in Meningiomas.: Kyeong Mee Park, Jin Ye Yoo, Hye Jae Cho; Korean J Pathol. 1999;33(4):274-280.

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Abstract PDF: Mutation of p53 tumor suppressor gene is now recognized as the most frequent genetic alteration in human neoplasms. Although meningiomas are common intracranial tumors, little is known about the clinical significance of p53 abnormalities in meningiomas. We studied 31 cases of meningioma to investigate the significance of p53 protein expression in meningiomas and its relationships with histological and clinical parameters and proliferative activity. Classical and atypical meningiomas were 16 (51.6%) and 15 cases (43.4%), respectively. p53 protein expression was detected in 4 (25.0%) of 16 classical, and 12 (80.0%) of 15 atypical meningiomas. p53 protein expression was correlated with Ki-67 staining index, atypical type, high histologic score, sheet pattern of the neoplastic cells, vascular proliferation, and male patient (p<0.05). In conclusion, immunohistochemical evaluation of p53 protein and histologic score of meningiomas are useful in assessing the prognosis.

Case Report

Nasal Inverted Papilloma Associated With Squamous Cell Carcinoma: A Report of Two Cases.: Mi Jin Gu, Dong Sug Kim, Young Kyung Bae, Yong Dae Kim; Korean J Pathol. 2001;35(3):248-281.

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Abstract PDF: Nasal inverted papilloma (IP) is a benign neoplasm that may be associated with squamous cell carcinoma (SCC). Several studies have suggested that human papilloma virus 16/18 (HPV 16/18) and p53 are closely related to the pathogenesis of IP with transformation to squamous cell carcinoma (IP-SCC). This study was conducted to investigate the role of HPV 16/18 and p53 in the pathogenesis of IP-SCC using immunohistochemistry. We studied two cases of IP-SCC and 10 cases of IP. None of the IP cases presented positivity for HPV 16/18 or p53 protein. Two cases of IP-SCC showed negative reactions for HPV 16/18. The SCC portion of the IP-SCC showed strong positivity for p53, while the IP portion of the IP-SCC was negative for p53. MIB-1 labeling index (LI) was estimated in the IP cases and the IP-SCC as well. In terms of MIB-1 LI, there was no statistical significance between IP and IP-SCC, and between the IP portion and the SCC portion in the cases of IP-SCC. In conclusion, we believe that alteration of the p53 protein is related to IP with malignant transformation, but further studies are required to investigate the correlation of HPV 16/18 and p53 in the pathogenesis of IP with malignant transformation, and the significance of the MIB-1 LI and p53 as biomarkers in IP.

Original Articles

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

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Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Expression of Cancer-Related Genes in Epstein Barr Virus-Infected Burkitt's Lymphoma Cell Line Treated with Mitomycin C.: Woo Bom Yeom, Seol Hee Park, Min Kyung Kim, Chul Hwan Kim, In Sun Kim, Dale Lee; Korean J Pathol. 2001;35(4):271-277.

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Abstract PDF: BACKGROUND
Infection of Epstein Barr virus (EBV) into B cells drives the infected cells into the cell cycle and frequently results in lymphoblastoid cells. Mitomycin C inhibits DNA synthesis of epithelial cells as well as lymphoid cells by cross-linking with DNA. Many of the cancer cells have various pathways for escaping the responsiveness to the negative growth-regulatory effects of mitomycin C and gaining the immortalized property. The auther performed a cell culture of an EBV infected Jijoye lymphoma cell line, and compared the cell cycle and cancer related genes between the mitomycin treated- and non-treated group.
METHODS
DNA and RNA were extracted from the Jijoye cells; and EBV nuclear antigen (EBNA)-1, 2 and latent membrane protein (LMP) of EBV and p53 and p21 mRNA analyse was performed.
RESULTS
Mitomycin C blocked G2/M phase, however, mitomycin did not affect the expression of EBNA-1, 2 and LMP. Mitomycin C also increased the p21 mRNA expression without p53 mRNA increase.
CONCLUSIONS
Mitomycin C induces B cell apoptosis by blocking the G2/M phase and by increasing p21 mRNA independent to p53, which reveals the presence of an alternative pathway of p21 induction by mitomycin C in EBV positive lymphoma cells

Human Papillomavirus Type 16, 18, and 33 Infection in Adenocarcinoma of the Uterine Cervix: Analysis of the p53 Gene Mutation and the Clincopathologic Correlation.: Kwang Sun Suh, Seong Jun Cho, Sun Young Na, Heung Tae Noh, Sang Ryun Nam; Korean J Pathol. 2004;38(5):295-300.

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Abstract PDF: BACKGROUND
Current evidence implicates specific types of the human papillomavirus (HPV) are involved in the development of cervical cancer. In HPV-negative cervical carcinomas, p53 mutation is thought to be a mechanism of oncogenesis. The purpose of this study was to evaluate the prevalence of p53 mutations in cervical adenocarcinomas and to investigate their correlation with HPV status and clinicopathologic parameters.
METHODS
A series of 38 primary cervical adenocarcinomas was analyzed for both HPV infection and p53 mutations. The HPV 16, 18, and 33 status was investigated by PCR amplification. The point mutations of the p53 gene were detected by the PCR-SSCP technique.
RESULTS
The prevalence of HPV 16, 18, or 33 infection was 73.7% (28/38). HPV 16 was present in 12 cases, HPV 18 was present in 15 cases, and HPV 33 was positive in one case. There was only one case that was positive for 18 as well as a p53 mutation in exon 6.
CONCLUSIONS
Our results indicate that HPV 18 infection was more common in cervical adenocarcinomas than HPV 16 infection. Mutant p53 was rarely found in cervical adenocarcinomas regardless of the type of HPV infection. There was no correlation between HPV infection and clinical stage or pathologic type of tumor.

Expression of p53 Protein and c-erbB-2 Oncoprotein in Breast Carcinoma.: Eun Hee Lee, Dong Sug Kim, Tae Sook Lee, Soo Jung Lee; Korean J Pathol. 1995;29(5):596-606.

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Abstract: This study was conducted to evaluate the expression of p53 and c-erbB-2 using immuno-histochemical methods in 145 primary breast carcinomas and to correlate it with other histo-pathological prognostic factors. Invasive ductal carcinoma represented 129 of the cases. Expression of p53 protein and c-erbB-2 oncoprotein was present in 48% (62/129) and 30% (39/129) of invasive ductal carcinomas, respectively. The expression of p53 protein was stongly associated with a high score of degree of differentiation (p<0.05), nuclear pleomorphism (p<0.05), mitotic index (p<0.05), SBR grade (p<0.05) and MSBR grade (p<0.05), but it was not associated with patient's age, size of tumor or axillary node metastasis. The overexpression of c-erbB-2 C-erbB-2 oncoprotein was strongly associated with a high score of nuclear pleomorphism and a high SBR grade (p<0.05), but not associated with patient's age, size of tumor, axillary node metastasis, degree of differentiation, mitotic index or MSBR grade. An inverse relationship between the expression of p53 protein and estrogen receptor status was found, but the expression of c-erbB-2 was not associated with estrogen receptor status. It is concluded that p53 protein and c-erbB-2 oncoprotein are important prognostic factors in breast cancers, and that the aberrant expression of p53 protein is the most useful prognostic factor becausd of strong association of known histopathological prognostic factors and negative estrogen receptor status.

K-ras Gene Mutations and Expression of K-ras, p16, Cyclin D1 and p53 in Synchronous Lesions of The Colon Adenoma-Carcinoma Sequences.: Hwa Eun Oh, Seong Jin Cho, Nam Hee Won, Dale Lee, Insun Kim, Bom Woo Yeom; Korean J Pathol. 2001;35(4):291-298.

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Abstract PDF: BACKGROUND
The colorectal adenoma-carcinoma sequence represents a well-known para-digm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma-carcinoma sequence has been well investigated, the studies about tumors of different dignity co-existent in the same patient are rare. K-ras mutation is an early genetic change in colon cancer. The genes involved in the cell cycle such as cyclin D1, p16, and p53 are important in the tumorigenesis of the colon. The aims of this study were to determine K-ras gene mutation and expression of K-ras, p16, cyclin D1 and p53 in synchronous lesions of the colon adenoma-carcinoma sequences and their possible relationship with K-ras mutation.
METHODS
The materials included 45 colonic adenocarcinomas which were accompanied by adenoma (22 low grade and 26 high grade). By using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), we detected K-ras mutation of codon 12. An aberrant K-ras, p16, cyclin D1 and p53 expressions were stained using an immunohistochemical method. RESULTS: K-ras mutation was 52.4% (11/21) of high grade adenomas. K-ras expression was 65.4% (17/26) of high grade adenomas. p16 and cyclin D1 expressions were 50% (11/22) and 90.9% (20/22) of low grade adenomas, respectively. p53 expression was 75.6% (34/45) of adenocarcinomas. There were statistical correlations among K-ras, p16 and cyclin D1.
CONCLUSIONS
These results indicate that the ras gene mutation is an early event and the overexpressions of p16, cyclin D1 and p53 are associated with K-ras mutation and expression in adenoma-carcinoma sequences.

The Aberrant Expression of p53 Protein in Liver Cell Carcinoma.: Woo Young Jang, Dong Sug Kim, Ki Kwon Kim, Tae Sook Lee, Chang Yoon Kim, Hong Jin Kim; Korean J Pathol. 1995;29(5):607-614.

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Abstract: This study was carried out to evaluate the aberrant expression of p53 protein using immunobistochemical method in 54 surgically resected liver cell carcinomas and to correlate it with clinical and pathological findings. Twenty five out of 54 cases(46%) showed positive reaction in the nucleus of liver cell carcinoma and negative reaction in associated 30 cases of cirrhosis, one case of adenoma and two cases of adenomatous hyperplasia. The p53 protein expression was associated with alpha-FP level(p<0.05), but not associated with HBsAg positivity. It was significantly associated with WHO classification, Edmondson-Steiner grade and nuclear grade p53(p<0.05), but not associated with tumor size, capsule formation, portal vein invasion, cirrhosis in surrounding tissue, Eggel classification, special cell type and mitosis. In conclusion, our results suggest that the aberrant expression of p53 protein can be an advisory factor, at least, for prognosis evaluation.

Expression of p53 Protein in Endometrial Carcinoma.: Mi Jin Kim, Dong Suk Kim; Korean J Pathol. 1999;33(5):347-352.

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Abstract PDF: The mutation of p53, a tumor suppressor gene, has been considered to play an important role in tumorigenesis in a variety of human cancers and the abnormal expression of p53 are frequently associated with poor prognosis. In order to examine the association of p53 overexpression with known prognostic factors including estrogen receptors (ER) and progesterone receptors (PR), we studied the status of p53 protein expression by immunohistochemical staining of paraffin sections of 29 endometrial carcinoma (25 endometrioid carcinoma, 2 clear cell carcinoma, and 2 serous carcinoma), obtained from hysterectomy. The results were as follows: The expression of p53, ER, and PR was present in 9/29 (31%), 3/29 (16%), and 12/29 (48%), respectively. The expression of p53 in endometrioid adenocarcinoma was present in 6/25 (24%) and showed significant correlation with histologic grade, nuclear grade, and myometrial invasion. The status of PR showed significant inverse correlation with histologic grade, nuclear grade and myometrial invasion. There was no significant correlation between ER status and these histologic factors. The expression of p53 was inversely associated with the status of PR, but statistically not significant. Our results indicate that p53 may be useful in predicting prognosis in endometrial carcinoma and will be able to provide helpful information in predetermination of aggressive behavior of the tumor in evaluation of curettage specimen.

Expression of p53 and nm23 Proteins in Non-Small Cell Lung Cancer.: Mi Seon Kwon, Won Il Kim, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1997;31(6):499-507.

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Abstract PDF: To elucidate the role of p53 and nm23 in the development, progression, and metastasis of non-small cell lung cancer, we studied 91 paraffin sections of the primary non-small-cell lung cancers and the 34 paraffin sections of their metastatic lymph nodes using the immunohistochemical method. The results are as follows: 1) The incidence of p53 protein expression was positively correlated with the staging of lung cancers (p<0.025). 2) The incidence of p53 protein expression was higher in the lung cancers with lymph node metastasis than in those without lymph node metastasis (p=0.009). 3) The incidence of nm23 protein expression was lower in the adenocacinomas than in the squamous cell carcinomas (p=0.032). 4) The incidence of nm23 protein expression was lower in the lung cancers with lymph node metastasis than in those without lymph node metastasis (p=0.026). The expression of nm23 protein between the primary lung cancers and corresponding metastatic lymph nodes showed positive correlation (Kendall's Tau-b correlation coefficient=0.47140, p=0.0068). 5) The expression of p53 was not correlated with the expression of nm23 protein (Kendall's Tau-b correlation coefficient=0.11387, p=0.2800). The above results suggest that an overexpression of p53 protein and a downregulation of nm23 protein are associated with tumor progression and metastasis in non-small-cell lung cancer.

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