The value of BRCA-1-associated protein 1 expression and cyclin-dependent kinase inhibitor 2A deletion to distinguish peritoneal malignant mesothelioma from peritoneal location of carcinoma in effusion cytology specimens

Our plain-English summary of The value of BRCA-1-associated protein 1 expression and cyclin-dependent kinase inhibitor 2A deletion to distinguish peritoneal malignant mesothelioma from peritoneal location of carcinoma in effusion cytology specimens, by W. Althakfi, S. Gazzo, M. Blanchet, et al (Cytopathology, 2020).

The study

• Authors: W. Althakfi, S. Gazzo, M. Blanchet, S. Isaac, E. Piaton, L. Villeneuve, O. Glehen, F.N. Gilly, M. Brevet
• Journal: Cytopathology
• Published: 2020;31(1):5-11
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Diffuse malignant peritoneal mesothelioma (DMPM), represents 30% of all malignant mesothelioma, and is characterised by a difficult diagnosis and different presentations. Immunohistochemistry has improved the diagnostic sensitivity and specificity in the differential diagnosis between metastatic adenocarcinoma and malignant mesothelioma, and loss of BRCA-1-associated protein 1 (BAP1) expression is correlated with BAP1 somatic or constitutional genetic defects. Furthermore, cyclin-dependent kinase inhibitor 2A (CDKN2A) is frequently lost in DMPM. In the present study, we assessed the value of integrating BAP1 in the panel of antibodies used for the diagnosis of DMPM in cytological samples. Since p16 fluorescent in situ hybridisation (FISH) assay could constitute an additional useful adjunct, results of BAP1 immunostaining and p16 FISH assays have been compared.

Methods: Forty-eight DMPM patients and 71 peritoneal carcinomatosis patients were included. BAP1 immunohistochemical and CDKN2A FISH techniques were performed on tissue specimens of DMPM (n = 48) and peritoneal carcinomatosis (n = 71) then on cell-block of DMPM (n = 16), peritoneal carcinomatosis (n = 25) and peritoneal benign effusion (n = 5).

Results: Loss of BAP1 expression was observed in 56.3% of DMPM while none of the peritoneal carcinoma specimens showed BAP1 loss of expression. CDKN2A loss was observed in 34.9% DMPM and 2.1% peritoneal carcinoma. Although BAP1 immunostaining was successful in 100% of cytological DMPM samples, CDKN2A deletion status could be obtained for 75% of DMPM cases.

Conclusion: BAP1 immunostaining represents an objective and reproducible diagnostic biomarker for peritoneal mesothelioma in effusion cytology specimens and should be preferred to CDKN2A FISH analysis on these precious samples.

© 2019 John Wiley & Sons Ltd.

In plain English

This laboratory study from Lyon University Hospital, France, compared two tests for telling diffuse malignant peritoneal mesothelioma (DMPM) apart from other cancers spread in the abdomen (peritoneal carcinomatosis) and from benign conditions, with a focus on cells taken from abdominal fluid. The authors tested tissue from 48 DMPM patients diagnosed from 2001 to 2015 and from 71 carcinomatosis patients. They also tested fluid samples (cell-blocks) from 16 DMPM, 25 carcinomatosis and 5 benign-effusion patients. Loss of the BAP1 protein was found in 27/48 (56.3%) DMPM tissue samples, which the authors note had been published before. It was also found in 9/16 (56.3%) DMPM fluid samples, matching the tissue result in every patient. No carcinomatosis or benign sample showed BAP1 loss. The CDKN2A gene test (FISH) found deletions in 15/43 (34.8%) DMPM tissue samples and 2/12 (16.7%) DMPM fluid samples, and could not be read in 4/16 DMPM fluid samples. The authors concluded that BAP1 staining should be preferred to CDKN2A FISH on fluid samples. Asbestos exposure was not studied.

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 laboratory study measuring the sensitivity and specificity of two tests (BAP1 immunostaining and CDKN2A FISH) on tissue and effusion cell-block samples
• Who was studied: Lyon University Hospital, France. All 48 diffuse malignant peritoneal mesothelioma cases diagnosed January 2001 to December 2015 (43 epithelioid, 3 biphasic, 2 sarcomatoid). Also 71 peritoneal carcinomatosis cases from 2014 and 2015 (43 digestive tract origin, 28 gynaecological origin) and 5 benign peritoneal effusions from 2015 as controls. Effusion cell-blocks were available for 16 mesothelioma, 25 carcinomatosis and 5 benign cases.
• Exposure: The article does not study asbestos or any other exposure. It evaluates two laboratory tests: BAP1 protein immunostaining and CDKN2A (p16) deletion by FISH.
• Main results:
  • In mesothelioma tissue samples, 27/48 (56.3%) showed loss of BAP1 protein expression. The authors note this tissue result had been previously published.
  • In the 16 mesothelioma fluid cell-block samples, BAP1 loss was seen in 9/16 (56.3%). CDKN2A loss was seen in 2/12 (16.7%) of those that could be tested. For all patients, the tissue and cell-block results were the same.
  • None of the peritoneal carcinomatosis samples showed BAP1 loss: 0/71 tissue samples and 0/25 cell-block samples. None of the 5 benign effusion samples showed BAP1 loss.
  • CDKN2A deletion was found by FISH in 15/43 (34.8%) mesothelioma tissue samples: 2 homozygous and 13 hemizygous.
  • Among carcinomatosis samples, one ovarian serous carcinoma showed monosomy of chromosome 9 (1/47 tissue samples, 2.1%), including its cell-block sample (1/16, 6.3%).
  • On cell-block samples, FISH could not be interpreted in 4/16 (25%) mesothelioma cases and 9/25 (36%) carcinoma cases. BAP1 staining was successful in all cell-block samples (16/16 mesothelioma, 25/25 carcinomatosis, 5/5 benign).
  • Combining both tests, BAP1 and/or CDKN2A alteration was found in 10/16 (62.5%) mesothelioma cell-block samples.
• The authors' conclusion: The authors concluded that BAP1 immunostaining would be an objective and reproducible diagnostic biomarker for peritoneal mesothelioma in effusion cytology specimens. They said it should be preferred to CDKN2A FISH on these samples, while noting that combining the two tests increases sensitivity.
• Limitations the authors state:
  • The authors suggested that the lower rate of CDKN2A deletion found in cytology samples may reflect the high FISH failure rate and the difficulty of recognising tumour cells by FISH, possibly giving false-negative results.
  • The authors stated that FISH is less sensitive, can be difficult to perform on cell-block samples, and is not available in all pathology departments.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Carcinoma, Cytology, Peritoneal Mesothelioma, Immunohistochemistry, Differential Diagnosis, Adenocarcinoma, BAP1.

Related studies

• Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens — K.B. Berg, A.M. Churg, et al. (2020)
• Diagnostic value of BRCA1-associated protein-1, glucose transporter-1 and desmin expression in the discrimination between reactive mesothelial proliferation and malignant mesothelioma in tissues and effusions — S. Önder, E. Özogul, et al. (2019)
• 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)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)
• BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas — N. Leblay, F. Leprêtre, et al. (2017)
• Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions — I. Cozzi, F.A. Oprescu, et al. (2018)

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