Utility of highly expressed EZH2 in pleural effusion cytology for the diagnosis of mesothelioma

Our plain-English summary of Utility of highly expressed EZH2 in pleural effusion cytology for the diagnosis of mesothelioma, by M. Yoshimura, M. Hamasaki, Y. Kinoshita, et al (Pathology International, 2020).

The study

• Authors: M. Yoshimura, M. Hamasaki, Y. Kinoshita, S. Matsumoto, A. Sato, T. Tsujimura, A. Iwasaki, K. Nabeshima
• Journal: Pathology International
• Published: 2020;70(10):831-833
• Type of article: Letter
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, the authors examined whether high expression of enhancer of zeste homolog 2 (EZH2), detected by immunohistochemistry (IHC), helped distinguish malignant pleural mesothelioma (MPM) from reactive mesothelial cells (RMC) in pleural effusion cytology cell blocks. They tested EZH2 alone and combined with BAP1 IHC, MTAP IHC and 9p21 fluorescence in situ hybridization (FISH). They studied 40 MPM cases (33 male, 7 female; mean age 69.8 years) and 20 RMC cases (11 male, 9 female; mean age 70.6 years). All were diagnosed between 2010 and 2019 at Fukuoka University Hospital and Hyogo College of Medicine, Japan. All RMC cases showed low EZH2 expression (<30%), while 45% of MPM cases showed high expression. Sensitivities were 57.5% for 9p21 FISH, 55.0% for BAP1 IHC, 55.0% for MTAP IHC and 45.0% for EZH2 IHC, each with 100% specificity. Combining EZH2 IHC with 9p21 FISH, BAP1 IHC or MTAP IHC gave sensitivities of 72.5%, 77.5% and 72.5%, respectively. Adding EZH2 IHC to BAP1 IHC plus 9p21 FISH or MTAP IHC raised sensitivity from 85% (34/40) to 87.5% (35/40). In six MPM cases, the other assays showed no abnormality; in one of these, high EZH2 expression helped diagnose MPM. The authors also described practical difficulties in evaluating IHC in cell blocks. They concluded that adding EZH2 IHC increased sensitivity in separating MPM from RMC. Because the sample was small, they said further validation was needed.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This letter to the editor reported a small study from two Japanese hospitals. It looked at laboratory tests for telling malignant pleural mesothelioma (MPM) apart from reactive mesothelial cells (RMC), a benign condition that can look similar under the microscope. The tests were run on cell samples taken from fluid around the lungs (pleural effusion). The authors examined samples from 40 MPM cases and 20 RMC cases diagnosed between 2010 and 2019. They asked whether high levels of a protein called EZH2, shown by staining, added anything to established tests: BAP1 staining, MTAP staining, and a genetic test for 9p21 deletion. Each test alone identified between 45.0% and 57.5% of the MPM cases, and none wrongly flagged an RMC case. Combining BAP1 with either 9p21 FISH or MTAP identified 85% (34/40) of MPM cases. Adding EZH2 raised this to 87.5% (35/40). The authors concluded that EZH2 staining is a potential candidate for addition to the diagnostic panel. They noted the small sample size and practical difficulties with cell samples. The article does not discuss asbestos exposure.

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: Letter to the editor reporting a diagnostic test study on stored pathology cases (pleural effusion cytology cell blocks)
• Who was studied: 40 malignant pleural mesothelioma cases (33 male, 7 female; mean age 69.8 years) and 20 reactive mesothelial cell cases (11 male, 9 female; mean age 70.6 years), diagnosed 2010 to 2019, from the pathology files of Fukuoka University Hospital and Hyogo College of Medicine, Japan
• Exposure: Asbestos exposure was not studied. The study evaluated laboratory diagnostic tests: EZH2 immunohistochemistry (IHC), BAP1 IHC, MTAP IHC and 9p21 FISH, alone and in combination.
• Main results:
  • EZH2 staining was low (below 30%) in all RMC cases. It ranged from 4.3% to 97.7% in MPM cases, and 45% of MPM cases showed high EZH2 expression.
  • Used alone, the tests detected these shares of MPM cases: 9p21 FISH 57.5% (23/40), BAP1 IHC 55.0% (22/40), MTAP IHC 55.0% (22/40) and EZH2 IHC 45.0% (printed as 18/20). Each test had 100% specificity.
  • Combined with EZH2 IHC, the detection rates in MPM cases were: with 9p21 FISH 72.5% (29/40), with BAP1 IHC 77.5% (31/40), and with MTAP IHC 72.5% (29/40).
  • High EZH2 did not correlate with the results of the other tests (P = 0.75, P = 0.54, P = 0.35). The authors gave this as the likely reason the combinations worked.
  • BAP1 IHC plus 9p21 FISH or MTAP IHC detected 85% (34/40) of MPM cases. Adding EZH2 IHC raised overall detection to 87.5% (35/40).
  • In six MPM cases, BAP1, MTAP and 9p21 tests were all normal. In one of these six, high EZH2 expression helped diagnose MPM.
• The authors' conclusion: The authors concluded that adding EZH2 IHC to the MPM diagnostic panel increased sensitivity for distinguishing MPM from RMC, and that it is a potential candidate for addition to the diagnostic panel. They suggested that combining BAP1, MTAP and EZH2 IHC would be useful in routine practice.
• Limitations the authors state:
  • The sample size was small, so further studies are needed to validate the usefulness of EZH2 IHC on effusion cell blocks.
  • Cell blocks, unlike tissue sections, cannot show tissue architecture or invasiveness.
  • Staining on cell blocks tends to be uneven, and tumor cells may be isolated or scattered, making them hard to identify.
  • A diagnosis based on EZH2 is sometimes held back when the share of EZH2-positive cells is close to the cutoff value.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Cytology, Mesothelioma, Immunohistochemistry, Pleural Mesothelioma, Reactive Mesothelial Cells, Cell Block, BAP1.

Related studies

• Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia — M. Yoshimura, Y. Kinoshita, et al. (2019)
• Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, M. Hamasaki, et al. (2021)
• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)
• The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions — C. Sadullahoglu, D. Nart, et al. (2017)
• Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma — A. Shinozaki-Ushiku, T. Ushiku, et al. (2017)
• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)

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