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Diagnostic Value Of The EZH2 Immunomarker In Malignant Effusion Cytology

Piao Piao Ang, G. C. Tan, N. Karim, Y. P. Wong
Published 2019 · Medicine

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Background: Differentiating reactive mesothelial cells from metastatic carcinoma in effusion cytology is a challenging task. The application of at least 4 monoclonal antibodies including 2 epithelial markers (Ber-EP4, MOC-31, CEA, or B72.3) and 2 mesothelial markers (calretinin, WT-1, CK5/6, or HBME-1) are often useful in this distinction; however, it is not readily available in many resource-limited developing countries. Aberrant immunoexpression of enhancer of zeste homolog 2 (EZH2), a transcriptional repressor involved in cancer progression, is observed widely in various malignancy. In this study, we evaluate the diagnostic value of EZH2 as a single reliable immunomarker for malignancy in effusion samples. Methods: A total of 108 pleural, peritoneal, and pericardial effusions/washings diagnosed as unequivocally reactive (n = 41) and metastatic carcinoma (n = 67) by cytomorphology over 18 months were reviewed. Among the metastatic carcinoma cases, 54 were adenocarcinoma and others were squamous cell carcinoma (n = 1), carcinosarcoma (n = 1), and carcinoma of undefined histological subtypes (n = 11). Cell block sections were immunostained by EZH2 (Cell Marque, USA). The percentages of EZH2-immunolabeled cells over the total cells of interest were calculated. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off score to define EZH2 immunopositivity. Results: A threshold of 8% EZH2-immunolabeled cells allows distinction between malignant and reactive mesothelial cells, with 95.5% sensitivity, 100% specificity, 100% positive predictive value, and 93.2% negative predictive value (p < 0.0001). The area under the curve was 0.988. Conclusion: EZH2 is a promising diagnostic biomarker for malignancy in effusion cytology which is inexpensive yet trustworthy and could potentially be used routinely in countries under considerable economic constraints.
This paper references
Differentiating reactive mesothelial cells from metastatic adenocarcinoma in serous effusions: The utility of immunocytochemical panel in the differential diagnosis
H. Saleh (2009)
Immunocytochemistry in effusion cytology
P. Fetsch (2001)
Value of CD15 immunostaining in diagnosing Hodgkin's disease: a review of published literature.
P. Hall (1987)
Diagnostic benefits of the combined use of liquid-based cytology, cell block, and carcinoembryonic antigen immunocytochemistry in malignant pleural effusion.
C. Woo (2018)
Use of a panel of markers in the differential diagnosis of adenocarcinoma and reactive mesothelial cells in fluid cytology.
E. C. Ko (2001)
Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma
A. Shinozaki-Ushiku (2017)
Challenges in the interpretation of peritoneal cytologic specimens.
O. Lin (2009)
EZH2, a unique marker of malignancy in effusion cytology
Huimiao Jiang (2014)
Diagnostic Utility of Epithelial Membrane Antigen (EMA) and Calretinin (CAL) in Effusion Cytology.
Neha Nautiyal (2017)
Diagnostic algorithm for determining primary tumor sites using peritoneal fluid
C. K. Park (2018)
Value of PAX8 and WT1 Immunostaining in Confirming the Ovarian Origin of Metastatic Carcinoma in Serous Effusion Specimens.
L. Zhao (2012)
The role of immunohistochemistry in the diagnosis of neoplastic pleural effusions.
M. Dinu (2012)
Immunocytochemical panel for distinguishing between adenocarcinomas and reactive mesothelial cells in effusion cell blocks
Jo-Heon Kim (2009)
Immunocytochemistry in the differential diagnosis of serous effusions
M. Lozano (2001)
Diagnostic value of monoclonal antibody B72.3 in detecting adenocarcinoma cells in serous effusions
A. F. Lauritzen (1989)
Roles of the EZH2 histone methyltransferase in cancer epigenetics.
J. Simon (2008)
Immunocytochemical utility of claudin‐4 versus those of Ber‐EP4 and MOC‐31 in effusion cytology
T. Oda (2016)
Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site
J. Sèlves (2018)
Utility of a limited panel of calretinin and Ber-EP4 immunocytochemistry on cytospin preparation of serous effusions: A cost-effective measure in resource-limited settings
R. Arora (2011)
Claudin‐4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology
V. Jo (2014)
Claudin 4 identifies a wide spectrum of epithelial neoplasms and represents a very useful marker for carcinoma versus mesothelioma diagnosis in pleural and peritoneal biopsies and effusions
F. Facchetti (2007)
HBME-1 immunostaining in reactive mesothelial versus metastatic adenocarcinoma cells in serous fluid.
Alireza Rahmani (2011)
Combined use of novel epithelial (MOC‐31) and mesothelial (HBME‐1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura
C. González-Lois (2001)
Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer
J. Choi (2010)
Distinct BMI-1 and EZH2 Expression Patterns in Thymocytes and Mature T Cells Suggest a Role for Polycomb Genes in Human T Cell Differentiation
F. Raaphorst (2001)
Value of claudin-4 immunostaining in the diagnosis of mesothelioma.
N. Ordóñez (2013)
Aberrations of EZH2 in Cancer
A. Chase (2011)
EZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-β1 and is a predictor of outcome in ovarian carcinoma patients. Carcinogenesis
Z Y Rao
Cytopathologic differential diagnosis of malignant mesothelioma, adenocarcinoma and reactive mesothelial cells: A logistic regression analysis
E. Çakır (2009)
Pleural, peritoneal and pericardial effusions
M Bibbo (2015)
Diagnostic problems in serous effusions
C. Bedrossian (1998)
Diagnostic accuracy of effusion cytology
H. Motherby (1999)
Diagnostic Accuracy of Ber-EP4 for Metastatic Adenocarcinoma in Serous Effusions: A Meta-Analysis
B. Wang (2014)
Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis
Ø. Fluge (2009)
Diagnostic yield of pleural fluid cytology in malignant effusions: an Australian tertiary centre experience
P. Loveland (2018)
Prognostic value of high EZH2 expression in patients with different types of cancer: a systematic review with meta-analysis
Tao Jiang (2016)
Performance Characteristics of Body Fluid Cytology Analysis of 344 380 Responses From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.
Z. Tabatabai (2018)
The importance of EZH2 and MOC‐31 expression in the differential diagnosis of benign and malignant effusions
C. Sadullahoğlu (2017)

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