Journal of Pathology and Translational Medicine

Review

Cervical intraepithelial neoplasia and cervical cytology in pregnancy: Ji-Young Kim, Jeong Yun Shim; J Pathol Transl Med. 2024;58(6):283-290. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.17

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Abstract PDF: Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.

Case Study

EWSR1 rearranged primary renal myoepithelial carcinoma: a diagnostic conundrum: Nilay Nishith, Zachariah Chowdhury; J Pathol Transl Med. 2023;57(5):284-288. Published online September 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.08.08

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Abstract PDF: Primary renal myoepithelial carcinoma is an exceedingly rare neoplasm with an aggressive phenotype and Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement in a small fraction of cases. In addition to its rarity, the diagnosis can be challenging for the pathologist due to morphologic heterogeneity, particularly on the biopsy specimen. At times, immunohistochemistry may be indecisive; therefore, molecular studies should be undertaken for clinching the diagnosis. We aim to illustrate a case of primary myoepithelial carcinoma of the kidney with EWSR1-rearrangement in a 67-year-old male patient who presented with right supraclavicular mass, which was clinically diagnosed as carcinoma of an unknown primary. An elaborate immunohistochemical work-up aided by fluorescent in-situ hybridization allowed us to reach a conclusive diagnosis. This unusual case report advocates that one should be aware of the histological mimickers and begin with broad differential diagnoses alongside sporadic ones and then narrow them down with appropriate ancillary studies.

Review

Trouble-makers in cytologic interpretation of the uterine cervix: Eunah Shin, Jaeeun Yu, Soon Won Hong; J Pathol Transl Med. 2023;57(3):139-146. Published online May 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.25

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Abstract PDF

The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.

Citations

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Risk of cervical stenosis after cervical excision in postmenopausal patients
Eva Hauge, Line Winther Gustafson, Mette Tranberg, Pinar Bor
European Journal of Obstetrics & Gynecology and Reproductive Biology.2025; 308: 208. CrossRef
Pitfalls in Gynecological Cytology: Review of the Common and Less Frequent Entities in Pap Test
Danijela Vrdoljak-Mozetič, Snježana Štemberger-Papić, Damjana Verša Ostojić, Roberta Rubeša, Marko Klarić, Senija Eminović
Acta Cytologica.2024; 68(3): 281. CrossRef
Cytological features of human papillomavirus‐infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2
Mitsuaki Okodo, Kaori Okayama, Koji Teruya, Ruku Shinohara, Shuichi Mizuno, Rei Settsu, Yasuyoshi Ishii, Masahiko Fujii, Hirokazu Kimura, Mizue Oda
Journal of Medical Virology.2023;[Epub] CrossRef

Original Articles

Diagnostic distribution and pitfalls of glandular abnormalities in cervical cytology: a 25-year single-center study: Jung-A Sung, Ilias P. Nikas, Haeryoung Kim, Han Suk Ryu, Cheol Lee; J Pathol Transl Med. 2022;56(6):354-360. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.09.05

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Abstract PDF

Background
Detection of glandular abnormalities in Papanicolaou (Pap) tests is challenging. This study aimed to review our institute’s experience interpreting such abnormalities, assess cytohistologic concordance, and identify cytomorphologic features associated with malignancy in follow-up histology.
Methods
Patients with cytologically-detected glandular lesions identified in our pathology records from 1995 to 2020 were included in this study.
Results
Of the 683,197 Pap tests performed, 985 (0.144%) exhibited glandular abnormalities, 657 of which had tissue follow-up available. One hundred eighty-eight cases were cytologically interpreted as adenocarcinoma and histologically diagnosed as malignant tumors of various origins. There were 213 cases reported as atypical glandular cells (AGC) and nine cases as adenocarcinoma in cytology, yet they were found to be benign in follow-up histology. In addition, 48 cases diagnosed with AGC and six with adenocarcinoma cytology were found to have cervical squamous lesions in follow-up histology, including four squamous cell carcinomas. Among the cytomorphological features examined, nuclear membrane irregularity, three-dimensional clusters, single-cell pattern, and presence of mitoses were associated with malignant histology in follow-up.
Conclusions
This study showed our institute’s experience detecting glandular abnormalities in cervical cytology over a 25-year period, revealing the difficulty of this task. Nonetheless, the present study indicates that several cytological findings such as membrane irregularity, three-dimensional clusters, single-cell pattern, and evidence of proliferation could help distinguishing malignancy from a benign lesion.

Citations

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Analysis of atypical glandular cells in ThinPrep Pap smear and follow-up histopathology
Tengfei Wang, Yinan Hua, Lina Liu, Bing Leng
Baylor University Medical Center Proceedings.2024; 37(3): 403. CrossRef

Evaluation of the characteristics of multiple human papillomavirus (HPV) infections identified using the BD Onclarity HPV assay and comparison with those of single HPV infection: Jinhee Kim, Moonsik Kim, Ji Young Park; J Pathol Transl Med. 2022;56(5):289-293. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.02

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Abstract PDF Supplementary Material

Background
Human papillomavirus (HPV) infection is a major cause of cervical cancer and associated precursor lesions. Multiple HPV genotype infections have been reported. However, their clinicopathological characteristics still remain elusive.
Methods
For this study, 814 consecutive patients who had undergone colposcopy and HPV genotyping test using BD Onclarity HPV assay were retrospectively selected. Clinicopathological parameters of multiple HPV infections were compared with those of single HPV infection.
Results
Multiple HPV infections were found in 110 out of 814 cases (13.5%). Multiple HPV infections were associated with a significantly higher incidence of high-grade intraepithelial lesions (HSILs) compared with single HPV infection. Other high-risk HPV genotypes, in addition to HPV 16, were found more frequently in the multiple HPV infections group; these included HPV 51, 52, 33/58, 56/59/66, and 35/39/68. No specific coinfection pattern was not identified. Additionally, the number of HPV genotypes in multiple HPV infections was not associated with the progression to HSIL or squamous cell carcinoma.
Conclusions
Multiple HPV infections have distinct clinicopathological characteristics (compared with single HPV infection). As their biological behavior is uncertain, close and frequent follow-up is warranted.

Citations

Citations to this article as recorded by

The Prevalence of Multi-Type Infections Among Human Papillomavirus Types in Korean Women
Jang Mook Kim, Hee Seung Song, Jieun Hwang, Jae Kyung Kim
Pathogens.2025; 14(4): 369. CrossRef
The cervical cancer related distribution, coinfection and risk of 15 HPV types in Baoan, Shenzhen, in 2017–2023
Rukai Li, Weiwei Meng, Yunhai Zuo, Yanli Xu, Shaonan Wu
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Francesca De Falco, Anna Cutarelli, Francesca Luisa Fedele, Cornel Catoi, Sante Roperto
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Patterns of single and multiple HPV infections in female: A systematic review and meta-analysis
Dan Zhou, Jing Xue, Yaqiong Sun, Liling Zhu, Ming Zhao, Meimei Cui, Min Zhang, Jingjing Jia, Limei Luo
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Age distribution of patients with multiple High-Risk Human Papilloma Virus (HR-HPV) genotypes and HPV vaccine recommendations by age
Gülçin Çetin Uysal, Nil Tekin
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Relative distribution of HPV genotypes in histological cervical samples and associated grade lesion in a women population over the last 16 years in Burgundy, France
Christelle Auvray, Serge Douvier, Odile Caritey, Jean-Baptiste Bour, Catherine Manoha
Frontiers in Medicine.2023;[Epub] CrossRef
Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions
Qinli Luo, Xianghua Zeng, Hanyi Luo, Ling Pan, Ying Huang, Haiyan Zhang, Na Han
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Prognostic Significance of CD109 Expression in Patients with Ovarian Epithelial Cancer: So Young Kim, Kyung Un Choi, Chungsu Hwang, Hyung Jung Lee, Jung Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Jae Ho Kim, Ki Hyung Kim, Dong Soo Suh, Byung Su Kwon; J Pathol Transl Med. 2019;53(4):244-252. Published online May 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.04.16

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Abstract PDF

Background
Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis.
Methods
Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy.
Results
CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001).
Conclusions
Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.

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Review

Pathogenesis of Focal Segmental Glomerulosclerosis: Beom Jin Lim, Jae Won Yang, Woo Sung Do, Agnes B. Fogo; J Pathol Transl Med. 2016;50(6):405-410. Published online October 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.21

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Abstract PDF

Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

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Original Articles

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma: Kijong Yi, Hyunsung Kim, Yumin Chung, Hyein Ahn, Jongmin Sim, Young Chan Wi, Ju Yeon Pyo, Young-Soo Song, Seung Sam Paik, Young-Ha Oh; J Pathol Transl Med. 2016;50(5):327-336. Published online August 31, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.22

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Abstract PDF

Background
Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown.
Methods
Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated.
Results
E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival.
Conclusions
Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

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The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
Journal of Gastrointestinal Cancer.2024; 55(2): 599. CrossRef
Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma
Ruizhi Wang, Yichao Zhu, Hao Zhong, Xinyue Gao, Qiang Sun, Meifang He
Frontiers in Oncology.2022;[Epub] CrossRef
Dysregulated paired related homeobox 1 impacts on hepatocellular carcinoma phenotypes
Weronika Piorońska, Zeribe Chike Nwosu, Mei Han, Michael Büttner, Matthias Philip Ebert, Steven Dooley, Christoph Meyer
BMC Cancer.2021;[Epub] CrossRef

Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients: Min-Kyung Yeo, Ahwon Lee, Soo Young Hur, Jong Sup Park; J Pathol Transl Med. 2016;50(4):294-299. Published online June 26, 2016; DOI: https://doi.org/10.4132/jptm.2016.05.09

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Abstract PDF

Background
Human papillomavirus (HPV) is a major risk factor for cervical cancer.
Methods
We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients.
Results
The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group.
Conclusions
The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.

Citations

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Human papilloma virus identification in ocular surface squamous neoplasia by p16 immunohistochemistry and DNA chip test
Tina Shrestha, Won Choi, Ga Eon Kim, Jee Myung Yang, Kyung Chul Yoon
Medicine.2019; 98(2): e13944. CrossRef
Comparison of the PANArray HPV Genotyping Chip Test with the Cobas 4800 HPV and Hybrid Capture 2 Tests for Detection of HPV in ASCUS Women
Eun Young Ki, Yoon Kyung Lee, Ahwon Lee, Jong Sup Park
Yonsei Medical Journal.2018; 59(5): 662. CrossRef

Significance of Parafibromin Expression in Laryngeal Squamous Cell Carcinomas: Inju Cho, Mija Lee, Sharon Lim, Ran Hong; J Pathol Transl Med. 2016;50(4):264-269. Published online June 23, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.24

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Abstract PDF

Background
Parafibromin is a product of the tumor suppressor gene that has been studied as a potential indicator of tumor aggressiveness in the parathyroid, breast, colorectum, and stomach. However, the clinical significance and potential function of parafibromin expression in head and neck squamous cell carcinomas remain largely unknown. The aim of this study was to evaluate the expression of parafibromin in laryngeal squamous cell carcinoma (LSCC) and to verify its potential as a biomarker of tumor behavior.
Methods
Parafibromin expression was evaluated in 30 cases of LSCC using immunohistochemistry. The correlations between parafibromin expression and clinicopathologic parameters were investigated.
Results
Parafibromin expression was positive in 15 cases (50%) and negative in 15 cases (50%). Tumor size and T stage showed a statistically significant inverse relationship with parafibromin expression (p=.028 and p<.001, respectively). Parafibromin expression was not associated with age, sex, lymph node metastasis, tumor differentiation, or tumor location. There was no statistically significant relationship between parafibromin expression and progression-free survival in the patients (p>.05).
Conclusions
Our results indicate that the downregulation or loss of parafibromin expression can be employed as a novel marker of tumor progression or aggressiveness in LSCC.

Citations

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CDC73 c.1155-3A>G is a pathogenic variant that causes aberrant splicing, disrupted parafibromin expression, and hyperparathyroidism-jaw tumor syndrome
Leor Needleman, Nicolette Chun, Sathvika Sitaraman, Marilyn Tan, Deborah E Sellmeyer, Electron Kebebew, Justin P Annes
JBMR Plus.2024;[Epub] CrossRef
Advances in the application of label‐free quantitative proteomics techniques in malignancy research
Xiao Meng, Dong Liu, Yan Guan
Biomedical Chromatography.2023;[Epub] CrossRef
The roles of the tumor suppressor parafibromin in cancer
Hua-chuan Zheng, Hang Xue, Cong-yu Zhang
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis
Hua-Chuan Zheng, Bao-Cheng Gong, Shuang Zhao
Oncotarget.2017; 8(56): 95270. CrossRef

Aquaporin 1 Is an Independent Marker of Poor Prognosis in Lung Adenocarcinoma: Sumi Yun, Ping-Li Sun, Yan Jin, Hyojin Kim, Eunhyang Park, Soo Young Park, Kyuho Lee, Kyoungyul Lee, Jin-Haeng Chung; J Pathol Transl Med. 2016;50(4):251-257. Published online June 7, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.30

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Abstract PDF

Background
Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial-mesenchymal transition (EMT) markers.
Methods
We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray.
Results
AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression- free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031).
Conclusions
AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma.

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Review

Dysembryoplastic Neuroepithelial Tumors: Yeon-Lim Suh; J Pathol Transl Med. 2015;49(6):438-449. Published online October 23, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.05

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Abstract PDF

Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneuronal neoplasm that most commonly occurs in children and young adults and may present with medically intractable, chronic seizures. Radiologically, this tumor is characterized by a cortical topography and lack of mass effect or perilesional edema. Partial complex seizures are the most common presentation. Three histologic subtypes of DNTs have been described. Histologically, the recognition of a unique, specific glioneuronal element in brain tumor samples from patients with medically intractable, chronic epilepsy serves as a diagnostic feature for complex or simple DNT types. However, nonspecific DNT has diagnostic difficulty because its histology is indistinguishable from conventional gliomas and because a specific glioneuronal element and/or multinodularity are absent. This review will focus on the clinical, radiographic, histopathological, and immunohistochemical features as well as the molecular genetics of all three variants of DNTs. The histological and cytological differential diagnoses for this lesion, especially the nonspecific variant, will be discussed.

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Original Articles

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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The Mechanism and Dynamic Regulation of Epithelial to Mesenchymal Transition in Ovarian Cancer
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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Alteration of the E-Cadherin/β-Catenin Complex Is an Independent Poor Prognostic Factor in Lung Adenocarcinoma: Hyojin Kim, Seol Bong Yoo, Pingli Sun, Yan Jin, Sanghoon Jheon, Choon Taek Lee, Jin-Haeng Chung; Korean J Pathol. 2013;47(1):44-51. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.44

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Abstract PDF

Background

Epithelial-mesenchymal transition (EMT) is an important step in the invasion and progression of cancer and in the development of chemoresistance by cancer cells.

Methods

To address the clinical significance of the EMT pathway in lung adenocarcinoma and the association of the pathway with histological subtype, we examined 193 surgically resected lung adenocarcinoma samples for the expression of representative EMT-related proteins (E-cadherin, β-catenin, and vimentin) by immunohistochemistry. Histological subtypes were classified according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The results for EMT-related protein expression were analyzed for correlation with clinicopathological features and with survival.

Results

The loss of E-cadherin expression and aberrant β-catenin expression were significantly associated with larger tumor size, pleural invasion, lymphatic/vascular invasion, and advanced pathological stage (p<0.05). The alteration of the E-cadherin/β-catenin complex was least frequently observed in the lepidic-predominant group, but these associations were not statistically significant. In the multivariate analysis, altered E-cadherin/β-catenin complex expression was found to be an independent poor prognostic factor (p=0.017; hazard ratio, 1.926; 95% confidence interval, 1.119 to 3.314).

Conclusions

The alteration of the expression of the E-cadherin/β-catenin complex was associated with aggressive tumor behavior in lung adenocarcinoma.

Citations

Citations to this article as recorded by

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Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers: Kyungbin Kim, Won Young Park, Jee Yeon Kim, Mee Young Sol, Dong Hun Shin, Do Youn Park, Chang Hun Lee, Jeong Hee Lee, Kyung Un Choi; Korean J Pathol. 2012;46(6):532-540. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.532

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Abstract PDF

Background

Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis.

Methods

Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC).

Results

CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers.

Conclusions

The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

Citations

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