Journal of Pathology and Translational Medicine

Original Articles

Upward trend in follicular lymphoma among the Korean population: 10-year experience at a large tertiary institution: Meejeong Kim, Hee Sang Hwang, Hyungwoo Cho, Dok Hyun Yoon, Cheolwon Suh, Chan Sik Park, Heounjeong Go, Jooryung Huh; J Pathol Transl Med. 2021;55(5):330-337. Published online September 2, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.25

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Background
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases.
Methods
We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes.
Results
The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066).
Conclusions
We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.

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Incidence Trend of Follicular Lymphoma in Taiwan Compared to Japan and Korea, 2001–2019
Liang-Chun Chiu, Chih-Wen Lin, Hung-Ju Li, Jian-Han Chen, Fu-Cheng Chuang, Sheng-Fung Lin, Yu Chang, Yu-Chieh Su
Journal of Clinical Medicine.2023; 12(4): 1417. CrossRef
A Case Report on the Complete Response of a Patient with Recurrent Follicular Lymphoma Treated with Integrative Medicine
Kyung-dug Park, Jisoo Kim, Yoona Oh, Beom-Jin Jeong, Yu-jin Jung, Sunhwi Bang
The Journal of Internal Korean Medicine.2023; 44(3): 585. CrossRef
Recent Updates on Diagnosis and Treatment of Follicular Lymphoma
Ga-Young Song, Deok-Hwan Yang
The Korean Journal of Medicine.2023; 98(5): 231. CrossRef
Classical Hodgkin lymphoma following follicular lymphoma: a case report
Bomi Kim
Journal of Yeungnam Medical Science.2023; 40(Suppl): S113. CrossRef
Incidence, clinicopathological features and genetics of in‐situ follicular neoplasia: a comprehensive screening study in a Japanese cohort
Naoki Oishi, Takahiro Segawa, Kunio Miyake, Kunio Mochizuki, Tetsuo Kondo
Histopathology.2022; 80(5): 820. CrossRef

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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Rare non-serous fallopian tube cancers: institutional experience and literature review
Dmitrii Sumtsov, Georgyi Sumtsov, Nataliia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Nataliia Kalashnik, Svitlana Smiian, Igor Gladchuk
Wiener Medizinische Wochenschrift.2024; 174(9-10): 199. CrossRef
UŞAQLIQ BORULARININ BİRİNCİLİ XƏRÇƏNGİ: DİAQNOSTİKASI VƏ MÜALİCƏSİNİN NƏTİCƏLƏRİ
D.G. Sumtsov, G.O. Sumtsov, N.I. Hyriavenko, S.A. Smiian, N.V. Kalashnyk, K.O. Sikora, N.M. Rozhkovska, I.Z. Gladchuk
Azerbaijan Medical Journal.2023; (4): 75. CrossRef
FEATURES OF ENDOMETRIUM STRUCTURE IN ALCOHOL-ABUSING HIV-INFECTED INDIVIDUALS
M. Lytvynenko
Inter Collegas.2021; 8(1): 52. CrossRef
Concurrent Clostridial Enteritis and Oviductal Adenocarcinoma with Carcinomatosis in an Adult Alpaca (Vicugna pacos)
Mandy Womble, Megan E. Schreeg, Allison Hoch, Enoch B. de Souza Meira, Derek Foster, Christopher Premanandan, Tatiane T. Negrão Watanabe
Journal of Comparative Pathology.2021; 189: 52. CrossRef
Problems of primary fallopian tube cancer diagnostics during and after surgery
D.G. Sumtsov, I.Z. Gladchuk, G.O. Sumtsov, N.I. Hyriavenko, M.S. Lyndin, V.V. Sikora, V.M. Zaporozhan
REPRODUCTIVE ENDOCRINOLOGY.2021; (59): 66. CrossRef

Smad1 Expression in Follicular Lymphoma: Jai Hyang Go; J Pathol Transl Med. 2015;49(3):243-248. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.03.30

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Abstract PDF: Background
Follicular lymphomas present with various immunohistologic patterns. The immunohistochemical markers used in the diagnosis of follicular lymphoma show variable degrees of sensitivity and specificity, and thus, additional germinal center markers are required. Smad1 has been reported to be overexpressed in follicular lymphoma, but little is known regarding the expression patterns of Smad proteins in human lymphoid tissue. Methods: In the present study, we performed immunohistochemistry for traditional germinal center markers and for Smad1 in human reactive lymphoid and follicular lymphoma tissues to investigate Smad1’s usefulness in the diagnosis of follicular lymphoma. Results: In the reactive germinal centers, most cells were positive for Smad1. Among the 27 follicular lymphoma cases, 17 of 21 (80%) were Smad1 positive, 17 of 27 (63%) were positive for CD10, and 23 of 27 (85%) were positive for Bcl6. Notably, three cases expressed CD10 only, and one only expressed Bcl6. All these cases were grade 3 tumors and showed follicular and diffuse growth patterns. Conclusions: These results indicate that Smad1 is a candidate as a germinal center marker. Furthermore, they suggest that the Smad signaling pathway might be involved in follicular lymphoma.

Prognostic Significance of BCL9 Expression in Hepatocellular Carcinoma: Jiyeon Hyeon, Soomin Ahn, Jae Jun Lee, Dae Hyun Song, Cheol-Keun Park; Korean J Pathol. 2013;47(2):130-136. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.130

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Abstract PDF

Background

BCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients.

Methods

We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months.

Results

Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078).

Conclusions

BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.

Citations

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The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities
Minjie Wu, Heng Dong, Chao Xu, Mengqing Sun, Haojin Gao, Fangtian Bu, Jianxiang Chen
Genes & Diseases.2024; 11(2): 701. CrossRef
The role of BCL9 genetic variation as a biomarker for hepatitis C-related hepatocellular carcinoma in Egyptian patients
Eman Abd El Razek Abbas, Ahmed Barakat Barakat, Mohamed Hassany, Samar Samir Youssef
Journal of Genetic Engineering and Biotechnology.2022; 20(1): 4. CrossRef
Molecular Targets and Signaling Pathways of microRNA-122 in Hepatocellular Carcinoma
Kwang-Hoon Chun
Pharmaceutics.2022; 14(7): 1380. CrossRef
Wnt/β-Catenin Signalling and Its Cofactor BCL9L Have an Oncogenic Effect in Bladder Cancer Cells
Roland Kotolloshi, Mieczyslaw Gajda, Marc-Oliver Grimm, Daniel Steinbach
International Journal of Molecular Sciences.2022; 23(10): 5319. CrossRef
Bcl9 Depletion Modulates Endothelial Cell in Tumor Immune Microenvironment in Colorectal Cancer Tumor
Zhuang Wei, Mei Feng, Zhongen Wu, Shuru Shen, Di Zhu
Frontiers in Oncology.2021;[Epub] CrossRef
Wnt Signaling Pathway Is among the Drivers of Liver Metastasis
Ivana Samaržija
Livers.2021; 1(4): 180. CrossRef
Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma
Myo Win Htun, Yasuaki Shibata, Kyaw Soe, Takehiko Koji
ACTA HISTOCHEMICA ET CYTOCHEMICA.2021; 54(6): 195. CrossRef
Wnt status-dependent oncogenic role of BCL9 and BCL9L in hepatocellular carcinoma
Nicole Huge, Maria Sandbothe, Anna K. Schröder, Amelie Stalke, Marlies Eilers, Vera Schäffer, Brigitte Schlegelberger, Thomas Illig, Beate Vajen, Britta Skawran
Hepatology International.2020; 14(3): 373. CrossRef
Structure and function of Pygo in organ development dependent and independent Wnt signalling
Yan Shi, Xiushan Wu, Shuoji Zhu, Huanlei Huang, Jian Zhuang, Haiyun Yuan, Wuzhou Yuan, Ping Zhu
Biochemical Society Transactions.2020; 48(4): 1781. CrossRef
BCL9/BCL9L in hepatocellular carcinoma: will it or Wnt it be the next therapeutic target?
Akshata Moghe, Satdarshan P. Monga
Hepatology International.2020; 14(4): 460. CrossRef
Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer
David M. Gay, Rachel A. Ridgway, Miryam Müller, Michael C. Hodder, Ann Hedley, William Clark, Joshua D. Leach, Rene Jackstadt, Colin Nixon, David J. Huels, Andrew D. Campbell, Thomas G. Bird, Owen J. Sansom
Nature Communications.2019;[Epub] CrossRef
Immunohistochemical Mapping of Bcl9 Using Two Antibodies that Recognize Different Epitopes Is Useful to Characterize Juvenile Development of Hepatocellular Carcinoma in Myanmar
Myat Thu Soe, Yasuaki Shibata, Myo Win Htun, Kuniko Abe, Kyaw Soe, Nay Win Than, Thann Lwin, Myat Phone Kyaw, Takehiko Koji
ACTA HISTOCHEMICA ET CYTOCHEMICA.2019; 52(1): 9. CrossRef
Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
Jing Wang, Mingjun Zheng, Liancheng Zhu, Lu Deng, Xiao Li, Linging Gao, Caixia Wang, Huimin Wang, Juanjuan Liu, Bei Lin
Cancer Cell International.2019;[Epub] CrossRef
SOX7 Suppresses Wnt Signaling by Disrupting β-Catenin/BCL9 Interaction
Rong Fan, HaiYan He, Wang Yao, YanFeng Zhu, XunJie Zhou, MingTai Gui, Jing Lu, Hao Xi, ZhongLong Deng, Min Fan
DNA and Cell Biology.2018; 37(2): 126. CrossRef
Hypoxia activates Wnt/β-catenin signaling by regulating the expression of BCL9 in human hepatocellular carcinoma
Wei Xu, Wang Zhou, Mo Cheng, Jing Wang, Zhian Liu, Shaohui He, Xiangji Luo, Wending Huang, Tianrui Chen, Wangjun Yan, Jianru Xiao
Scientific Reports.2017;[Epub] CrossRef
Hepatocellular carcinoma biology predicts survival outcome after liver transplantation in the USA
Mohamed Abd El-Fattah
Indian Journal of Gastroenterology.2017; 36(2): 117. CrossRef
miR-30a acts as a tumor suppressor by double-targeting COX-2 and BCL9 in H. pylori gastric cancer models
Xuan Liu, Qing Ji, Chengcheng Zhang, Xiaowei Liu, Yanna Liu, Ningning Liu, Hua Sui, Lihong Zhou, Songpo Wang, Qi Li
Scientific Reports.2017;[Epub] CrossRef
BCL9, a coactivator for Wnt/β-catenin transcription, is targeted by miR-30c and is associated with prostate cancer progression
XIAO-HUI LING, ZHI-YUN CHEN, HONG-WEI LUO, ZE-ZHEN LIU, YING-KE LIANG, GUAN-XING CHEN, FU-NENG JIANG, WEI-DE ZHONG
Oncology Letters.2016; 11(3): 2001. CrossRef

Expression of Human Papillomavirus-Related Proteins and Its Clinical Implication in Tonsillar Squamous Cell Carcinoma: Joon Seon Song, Min-Sik Kim, Joon Wook Park, Youn Soo Lee, Chang Suk Kang; Korean J Pathol. 2012;46(2):177-186. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.177

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Abstract PDF

Background

Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We examined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC.

Methods

Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV.

Results

Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1).

Conclusions

Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.

Citations

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Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea
Hyun Woong Jun, Yong Bae Ji, Chang Myeon Song, Jae Kyung Myung, Hae Jin Park, Kyung Tae
Frontiers in Surgery.2022;[Epub] 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
In situ hybridization for high risk HPV E6/E7 mRNA in oropharyngeal squamous cell carcinoma
Krish Suresh, Parth V. Shah, Sydney Coates, Borislav A. Alexiev, Sandeep Samant
American Journal of Otolaryngology.2021; 42(1): 102782. 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
Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists
James S. Lewis, Beth Beadle, Justin A. Bishop, Rebecca D. Chernock, Carol Colasacco, Christina Lacchetti, Joel Todd Moncur, James W. Rocco, Mary R. Schwartz, Raja R. Seethala, Nicole E. Thomas, William H. Westra, William C. Faquin
Archives of Pathology & Laboratory Medicine.2018; 142(5): 559. CrossRef
Detection of HPV infection in head and neck cancers: Promise and pitfalls in the last ten years: A meta-analysis
Carolin G�tz, Clara Bischof, Klaus-Dietrich Wolff, Andreas Kolk
Molecular and Clinical Oncology.2018;[Epub] 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
Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma
Yoon Ho Ko, Hye Sung Won, Der Sheng Sun, Ho Jung An, Eun Kyoung Jeon, Min Sik Kim, Han Hong Lee, Jin Hyoung Kang, Chan Kwon Jung
Pathology International.2014; 64(10): 499. CrossRef
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 Journal of Pathology.2013; 47(2): 148. CrossRef

Case Reports

In Situ Follicular Lymphoma Developed after Hodgkin Lymphoma.: Ho Sung Park, Sang Jae Noh, Jae Yong Kwak, Eun Kee Song, Myung Hee Sohn, Ho Lee, Woo Sung Moon, Kyu Yun Jang; Korean J Pathol. 2011;45:S53-S57.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S53

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Abstract PDF: In situ follicular lymphoma is a newly defined entity among the lymphoid neoplasms and is defined as architecturally normal-appearing lymph nodes and other lymphoid tissues that have one or more follicles that demonstrate bcl-2 overexpressing centrocytes and centroblasts, with or without a monomorphic cytologic appearance suggestive of follicular lymphoma. Here we present a case of in situ follicular lymphoma diagnosed during the follow-up after a complete response to the treatment of lymphocyte-rich classical Hodgkin's lymphoma. In our case, because only a few germinal centers contained bcl-2 overexpressing cells, we missed the diagnosis of in situ follicular lymphoma in the initial histological examination. We could establish the diagnosis only after performing bcl-2 immunostaining in the sequential biopsy. Therefore, we recommend that careful histological examination along with bcl-2 immunostaining is needed in patients with suspicious clinical findings.

Solitary Fibrous Tumor of the Conjunctiva with Heretofore Undescribed Pathologic Findings.: Na Rae Kim, Jae Y Ro, Kyung Hwan Shin, Hae Jung Paik, Jung Suk An, Seung Yeon Ha; Korean J Pathol. 2011;45(3):315-318.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.315

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Abstract PDF

A 37-year-old female presented with a conjunctival mass discovered 3 years prior. An excisional biopsy revealed a patternless proliferation of round and spindle-shaped cells with an eosinophilic fibrillary cytoplasm and vesicular nuclei with occasional inclusions. Psammoma bodies were arranged around the dilated irregularly-shaped vessels. Differential diagnoses included conjunctival solitary fibrous tumor (SFT), nevus, glomangioma, ectopic meningioma, and mesectodermal leiomyoma. The tumor cells were immunoreactive for CD34, CD99, bcl-2 and vimentin, and were negative for smooth muscle actin, desmin, glial fibrillary acidic protein, S-100 protein, epithelial membrane antigen, and human melanoma black-45. Ultrastructurally, the tumor cells had rough endoplasmic reticulum, free ribosomes, and scattered mitochondria without basal lamina or cellular junctions, which are features of fibroblasts. A diagnosis of SFT was rendered based on the light microscopic, immunohistochemical, and electron microscopic findings. We report here on the second case of a SFT arising in the conjunctiva, which clinically and histologically mimics conjunctival nevus, glomangioma, ectopic meningioma, and a hybrid neurogenic-myogenic tumor such as mesectodermal leiomyoma.

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Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis
Nayoung Han, Hannah Kim, Soo Kee Min, Sun-Ha Paek, Chul-Kee Park, Seung-Hong Choi, U-Ri Chae, Sung-Hye Park
Journal of Pathology and Translational Medicine.2016; 50(2): 113. CrossRef

Original Articles

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.

Distinction of Pulmonary Large Cell Neuroendocrine Carcinoma from Small Cell Lung Carcinoma Using a Panel of Bcl-2, p63, and 34betaE12.: Jun Zhe Li, Chan Choi, Yoo Duk Choi, Kook Joo Na; Korean J Pathol. 2011;45(2):170-174.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.170

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Abstract PDF: BACKGROUND
Making the distinction between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is difficult in some samples of biopsy tissues, but we have to separate LCNEC from SCLC because the two types of cancer may need different therapy and they have different prognostic implications. Thus far, there are no specific immunohistochemical markers that allow distinguishing these two kinds of tumors.
METHODS
We performed an immunohistochemical analysis to study the expressions of p63, Bcl-2, and 34betaE12 and to investigate whether these 3 molecules have correlations in LCNEC and SCLC. We also evaluated the expression of the neuroendocrine markers chromogranin, synaptophysin and CD56.
RESULTS
A statistical analysis was performed for p63, Bcl-2, and 34betaE12 in separate and combined panels. According to the combinations of p63, Bcl-2, and 34betaE12, there were frequent expressions of p63-/Bcl-2+ or Bcl-2+/34betaE12- in the SCLC, and there was a superior proportion of them in the SCLC rather than that in the LCNEC. The p63-/Bcl-2+ and Bcl-2+/34betaE12- antibody combinations showed higher specificities compared to any single antibody for diagnosing SCLC.
CONCLUSIONS
Bcl-2 and selective p63 or 34betaE12 made up a most useful panel of markers for making the differential diagnosis of LCNEC and SCLC.

p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors.: Seok Ju Park, Woo Jung Sung, Mi Jin Kim; Korean J Pathol. 2010;44(6):597-604.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.597

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Abstract PDF

BACKGROUND
At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated.
METHODS
A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed.
RESULTS
Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011).
CONCLUSIONS
High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

Citations

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Over-expression of β-catenin is associated with high grade of prostatic cancer in Libyan patients
W. Said, F. Emaetig, K. El Gehani, T. Eldarat, A. Buhmeida, N. Enattah, A. Elzagheid, O. Al-Fituri
African Journal of Urology.2017; 23(2): 133. CrossRef
Bcl2 en cáncer avanzado de próstata y asociación con resistencia a la castración
R.F. Velázquez-Macías, F.E. De La Torre-Rendón, G. Ramos-Rodríguez, C.A. Calzada-Mendoza, R.M. Coral-Vázquez
Revista Mexicana de Urología.2016; 76(5): 288. CrossRef
Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer: A retrospective study from the view point of new 2010 anatomic stage/prognostic groups
Tae‐Jung Kim, Ji Youl Lee, Tae‐Kon Hwang, Chang Suk Kang, Yeong‐Jin Choi
Journal of Surgical Oncology.2011; 104(5): 472. CrossRef

Expression of P-glycoprotein and Apoptosis in Diffuse Large B-cell Lymphoma.: Ji Eun Kim, Young A Kim, Mee Soo Chang, Yunkyeong Jeon, JinHo Paik, Seon Og Yoon; Korean J Pathol. 2009;43(4):317-320.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.317

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Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma which responds well to conventional chemotherapy. However, quite a few patients have a recurrence with more aggressive forms after completion of therapy. Multidrug resistance proteins (MRP) are related to this process in several ways such as cell cycle alteration and modulation of apoptosis. METHODS: We investigated the expression of P-glycoprotein (Gp), one of the well-known MRP, as well as apoptosis associated proteins in DLBCL. Immunohistochemical staining for Gp, p53, Bcl-2, Ki-67, active caspase 3 and FADD was done in forty DLBCL cases. The association between MRP and apoptosis associated proteins to clinical findings was also tested. RESULTS: Twenty-nine patients out of 40 (73%) with DLBCL were positive for Gp, and 26 cases (65%) had a strong positive for Gp. Gp expression was stronger in high-grade lesions than in low-grade lesions and was associated to Bcl-2 expression. However, we could not find an adverse impact of Gp expression on patients' overall survival or relapse free survival rate. CONCLUSIONS: Our study revealed a high frequency of expression for Gp in DLBCL with a possible relationship between the expressions of Gp to apoptosis associated proteins.

Expression Patterns of Bcl-2 and PCNA in Cervical Intraepithelial Neoplasia.: Mee Sook Roh, Gi Yeung Huh, Sook Hee Hong; Korean J Pathol. 1995;29(6):703-713.

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Abstract PDF: Immunohistochemical stains for bcl-2 oncoprotein and PCNA and examination of the mitosis level were perfon-ned in 76 cases of cervical intraepithelial neoplasia (CIN). We studied the expression pattern of bcl-2 protein according to histologic grades and the function of bcl-2 oncogene associated with cellular proliferation by comparing with PCNA expression and the mitosis level. The results were as follows: 1) Of 76 cervical intraepithelial neoplasias, 23 (30.3%) were CIN I, 23 (30.3%) were CIN II, and 30 (39.4%) were CIN III. 2) Of 23 CIN I cases, grade 0 and 1 mitosis level were seen in 20 (87.0%), PCNA in 16 (69.6%), and bcl-2 in 19 (82.6%) cases, respectively, which indicates that CIN I lesions have a low cellular proliferative activity. 3) Of 30 CIN III cases, grade 2 and 3 mitosis level were noted in 28 (93.3%), PCNA in 25 (83.3%) and bcl-2 in 19 (63.3%) cases, respectively, which indicates that CIN III lesions have a high cellular proliferative activity. The results suggest that progressive increase of dysfunctional proliferative activity and abnormal decrease of cell death result in increased number of neoplastic cells according to CIN grade. Also the expression rate of bcl-2, PCNA and mitosis level were significantly different between CIN I and 111, which suggest that they might be good parameters for classifying CIN into low and high grade and for prediction of the biologic behavior of the CIN lesion.

The Studies of bcl-2 Oncoprotein and Epstein-Barr Virus Expression in Malignant Lymphomas: Immunohistochemical and in situ hybridization analysis on 66 cases.: Hye Jae Cho, Yeon Mee Kim, Hyun Ju Yoo, Jong Eun Joo; Korean J Pathol. 1996;30(2):121-131.

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Abstract PDF: Bcl-2 oncoprotein is being localized to mitochondria and interfering with programmed cell death (apoptosis) independent of promoting cell division in the lymphoid and nonlymphoid cells. The bcl-2 oncoprotein expression has been reported in follicular lymphomas as well as in diffuse non-Hodgkin's lymphoma, leukemia and a variable propotion of Hodgkin's lymphoma cases. Recent evidence suggests that some lymphomas protected from apoptosis is conferred through expression of Epstein-Barr virus(EBV) latent membrane protein which turn to cause upregulation of bcl-2. To define the role of the bcl-2 oncoprotein and EBV in lymphoid malignancy, we tried immunohistochemical studies with anti-bcl-2 antibody and In situ hybridization (ISH) with EBV-encoded small nuclear RNAs(EBER) in the paraffin embedded sections of 46 non-Hodgkin's lymphoma (NHL) cases and 20 Hodgkin's lymphoma (HL) cases. Bcl-2 oncoprotein expression was found in 37 of 46 cases (80%) of NHL with relatively strong cytoplasmic staining, and in 14 of 20 cases (70%) of HL with weak cytoplasmic staining in limited small numbers of RS, Hodgkin and lacunar cells. The widespread presence of bcl-2 oncogene in many different types of both NHL and HL supports that the extended cell survival through overexpression of bcl-2 gene protein may be a growth advantage of neoplastic lymphoid cells. In the ISH analysis for EBV, the presence of EBV was detected in 17 of 20 cases (85%) of HL, compared to 6 of 44 cases(13.6%) of NHL. It appears to be no direct correlation between overexpression of bcl-2 oncoprotein by neoplastic lymphoid cells and the presence of EBV in NHL but it seems to be a definite association between EBV and HL.

A Study of Bcl-2 Oncoprotein Expression in Endometrial Carcinoma Correlated with Hormone Receptor Status.: Young Im Han, Hye Jin Lee, Ji Yeon Lee, Sun Kyung Lee; Korean J Pathol. 1996;30(5):408-416.

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Abstract PDF: Bcl-2 is a proto-oncogene initially described in follicular lymphoma, associated with chromosomal translocation(14;18). Recent studies have shown the presence of Bcl-2 in nonhematolymphoid tissue, especially in hormonally responsive tissue. The endometrium is an attractive model for studying the hormone dependent regulation of Bcl-2 expression. We have studied the immunoreactivity of Bcl-2 oncoprotein in relation to the immunoreactivity of estrogen receptors(ER) and progesterone receptors(PR) by immunohistochemistry in 52 human endometrial carcinomas, according to nuclear grade. The results obtained are summarized as followings, 1) Immunohistochemical grade of Bcl-2 showed a significant inverse correlation with nuclear grade. 2) Immunohistochemical grades of ER and PR also showed a significant inverse correlation with nuclear grade, and were well correlated with each other. 3) Immunohistochemical grades of Bcl-2 and hormone receptors showed a strongly significant correlation. On the basis of the above results, we suggest that Bcl-2 expression may be under hormone dependent control and that it can be used in prognosis and choice of hormonal therapy in the presence of hormone receptor.

Detection of bcl-2/IgH Gene Rearrangement and Expression of c-myc and p53 Oncoprotein in B-cell Lymphoma.: Ghee Young Kwon, Chul Woo Kim; Korean J Pathol. 1996;30(5):437-446.

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Abstract PDF: Many kinds of genetic changes have been known to be associated with malignant lymphoma and bcl-2, p53 and c-myc are some examples. We investigated the expression of p53 and c-myc protein in follicular and diffuse B cell lymphoma by immunohistochemistry to study the possible role of these proteins in the lymphomagenesis and transformation of the tumor. The rearrangement of bcl-2 oncogene and the immunoglobulin heavy chain gene was searched for in those cases by polymerase chain reaction(PCR). Paraffin-embedded tissues of fifteen follicular lymphomas and 14 diffuse lymphoma cases were used. The results of immunohistochemical staining are summarized as follows: 1) p53 positivity is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.001); 2) c-myc expression is not increased in diffuse lymphoma compared with follicular lymphoma; 3) PCNA index is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.03) but there was no statistically significant correlation between PCNA index and p53 positivity(P=0.44); 4) Eight out of 14 cases of follicular lymphoma and 12 of 14 cases of diffuse lymphoma showed rearrangement of the immunogloblulin heavy chain gene; 5) bcl-2 oncogene rearrangement was identified in only one case of follicular lymphoma and all the diffuse type lymphomas were negative in bcl-2/IgH rearrangement. In conclusion, assuming that the follicular pattern of B-cell lymphoma often transforms to diffuse type in later stages, c-myc over-expression might be an earlier event than p53 mutation in the process of tumor progression in B-cell lymphoma. bcl-2/IgH gene rearrangement in follicular lymphoma is a rare finding in Korea compared to that of Western countries.

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