The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions

Our plain-English summary of The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions, by C. Sadullahoglu, D. Nart, A. Veral (Diagnostic Cytopathology, 2017).

The study

• Authors: C. Sadullahoglu, D. Nart, A. Veral
• Journal: Diagnostic Cytopathology
• Published: 2017;45(2):118-124
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: All malignant tumors may spread throughout the pleural, peritoneal, and pericardial cavities. The presence of tumor cells in serosal fluid is a poor prognostic indicator. It may be difficult to differentiate nuclear atypia of mesothelial cells due to injury of serosal surfaces from mesothelioma or malignant epithelial tumor cells. Epithelial and mesothelial immunohistochemical markers can be used in such conditions. The aim of this study was to evaluate the expression of two immunohistochemical markers (MOC-31 and EZH2) in serosal effusions.

Methods: The study included a total of 142 patients diagnosed with benign or malignant cytology between January 2012 and April 2014. MOC-31 and EZH2 were applied to the cell blocks of 53 patients with benign cytology and 89 patients with malignant cytology determined based on the clinical, radiological data, histopathology diagnosis, and clinical follow-up in the absence of any surgical material of the patient in the hospital archive system.

Results: None of the benign cases showed MOC-31 and EZH2 expression, although these markers were positive in 96 and 93% respectively of the malignant cases.

Conclusion: In conclusion, it could be considered cost-effective to use a double immunohistochemical antibody kit for these two markers, MOC-31 membranous and EZH2 nuclear staining, in the diagnosis of malignant effusions. Diagn. Cytopathol. 2017;45:118-124. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.

In plain English

This laboratory study, from the Pathology Department of Ege University School of Medicine in Turkey, tested whether two stains, MOC-31 and EZH2, could tell cancer cells apart from benign (reactive) lining cells in fluid that had built up around the lungs or in the abdomen. The authors stained cell samples from 142 patients seen between January 2012 and April 2014: 53 with benign fluid and 89 with cancer cells in the fluid, most often from cancers of the ovary, lung and breast. Only one of the cancer patients had mesothelioma, of the peritoneum. The study did not look at asbestos exposure. None of the 53 benign samples showed staining for either marker in their lining cells. Among the 89 cancer samples, 93% stained with EZH2 and 96% with MOC-31. The peritoneal mesothelioma was negative for MOC-31 and positive for EZH2. EZH2 also stained inflammatory cells. In this series, the two markers used together picked up every cancer sample. The authors concluded that a single kit combining both stains could be cost-effective. They said one mesothelioma case was not enough for further comment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic study of two immunohistochemical stains (EZH2 and MOC-31) applied to archived cell blocks from benign and malignant effusions, with the slides read without diagnostic information
• Who was studied: 142 serosal effusions from 142 patients (61 males, 81 females) evaluated at the Pathology Department of Ege University School of Medicine, Turkey, between January 2012 and April 2014. There were 47 abdominal and 95 pleural fluid samples. 53 patients had benign cytology (mean age 54, range 9 to 91) and 89 had malignant cytology (mean age 59, range 41 to 80). The commonest primary sites in the malignant group were ovary (28), lung (21) and breast (15). One patient had peritoneal mesothelioma.
• Exposure: Not an exposure study. Asbestos exposure was not assessed. What was studied was staining for two markers: nuclear EZH2 and membranous MOC-31. Nuclear EZH2 staining was counted as positive when more than 5% of tumor or mesothelial cells stained.
• Main results:
  • Benign group: none of the 53 patients showed EZH2 or MOC-31 expression in mesothelial cells.
  • Malignant group: of 89 patients, 93% (83) showed EZH2 expression and 96% (86) showed MOC-31 expression.
  • MOC-31 was negative, but EZH2 positive, in 1 metastatic renal cell carcinoma, 1 urothelial carcinoma and 1 mesothelioma (peritoneal).
  • EZH2 was negative in 6 malignant cases (1 lung adenocarcinoma, 3 ovarian surface epithelial tumors, 1 ovarian tumor of unknown subtype, 1 pancreatic adenocarcinoma). All 6 were MOC-31 positive.
  • Both markers stained the malignant group significantly more than the benign group (P less than 0.001).
  • Sensitivity and specificity were 93% and 100% for EZH2, and 96% and 100% for MOC-31. Positive predictive value was 100% for both. Negative predictive values were 89% for EZH2 and 94% for MOC-31. The table gives 100% for all four measures when the two markers were combined.
  • In both benign and malignant samples, inflammatory cells showed nuclear EZH2 staining and no MOC-31 staining.
• The authors' conclusion: The authors concluded that a double immunohistochemical kit for MOC-31 (membranous) and EZH2 (nuclear) staining could be considered cost-effective for diagnosing malignant effusions. They added that EZH2 should be assessed together with MOC-31 where inflammatory cells also stain.
• Limitations the authors state:
  • Only one mesothelioma case was included, which the authors said was not enough for further comment.
  • Only one effusion from metastatic urothelial carcinoma was studied.
  • EZH2 also stains inflammatory cells, which limits its use where tumor cells are loosely scattered among inflammatory cells.

Topics

Medical terms in this study, explained in our Lexicon: MOC-31, Differential Diagnosis, Pericardial, Nuclear Atypia, Mesothelial Cells, Serosal Surface, Mesothelioma, Cytology.

Related studies

• Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry — X.Y. Su, G.D. Li, et al. (2011)
• Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology — T. Oda, S. Ogata, et al. (2016)
• IMP3/L523S, a novel immunocytochemical marker that distinguishes benign and malignant cells: the expression profiles of IMP3/L523S in effusion cytology — K. Ikeda, G. Tate, et al. (2010)
• A case of malignant mesothelioma pleural effusion with MOC-31, BerEP4, and calretinin expression — P. Zhao (2019)
• Detection of cancer cells in effusions from patients diagnosed with gynaecological malignancies. Evaluation of five epithelial markers — B. Davidson, B. Risberg, et al. (1999)
• MMP-7 is a highly specific negative marker for benign and malignant mesothelial cells in serous effusions — B. Davidson, H.T. Stavnes, et al. (2016)

Browse more research in Diagnostic Cytopathology, or return to medical research.