Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma

Our plain-English summary of Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma, by D. Wu, K. Hiroshima, T. Yusa, et al (Annals of Diagnostic Pathology, 2017).

The study

• Authors: D. Wu, K. Hiroshima, T. Yusa, D. Ozaki, E. Koh, Y. Sekine, S. Matsumoto, K. Nabeshima, A. Sato, T. Tsujimura, H. Yamakawa, Y. Tada, H. Shimada, M. Tagawa
• Journal: Annals of Diagnostic Pathology
• Published: 2017;26:31-37
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.

Copyright © 2016 Elsevier Inc. All rights reserved.

In plain English

This laboratory study examined tumor tissue from 38 people in Japan with pleural mesothelioma, a cancer of the lining around the lungs. Under the microscope it can be hard to tell a biphasic tumor, which contains both epithelioid and spindle-shaped sarcomatoid cancer cells, from an epithelioid tumor surrounded by unusual-looking fibrous tissue. The authors tested whether two lab tests helped. One was FISH, which detects loss of the p16/CDKN2A gene. The other was BAP1 staining. Using these results, 28 cases were classified as 19 biphasic and 9 epithelioid mesotheliomas. In 18 of 19 biphasic tumors (94.7%), both components showed homozygous deletion of p16/CDKN2A, meaning loss of both copies of the gene. Counting 10 more biphasic cases, the total was 28 of 29 (96.6%). Seven of 9 epithelioid tumors (77.8%) had this deletion, but none of the 7 stromal samples tested did. BAP1 loss was found in 5 of 13 biphasic and 5 of 9 epithelioid tumors, but not in the stroma of the epithelioid tumors. The authors concluded the two tests are helpful for telling these tumor types apart. The study did not report 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: Laboratory diagnostic study of archived tumor tissue: FISH for p16/CDKN2A deletion and BAP1 immunohistochemistry
• Who was studied: 38 pleural mesotheliomas. 28 were from Tokyo Women's Medical University Yachiyo Medical Center, Chiba Rosai Hospital and Chiba East Hospital, diagnosed between 2007 and 2015; 20 of these were cases where biphasic and epithelioid mesothelioma were hard to tell apart. The other 10 were biphasic mesotheliomas from Fukuoka University Hospital and Hyogo Medical University Hospital.
• Exposure: Not reported. The study examined genetic and protein changes in tumor tissue, not asbestos or other exposures.
• Main results:
  • Using the test results, the 28 cases were classified as 19 biphasic mesotheliomas and 9 epithelioid mesotheliomas with atypical fibrosis
  • 18 (94.7%) of 19 biphasic mesotheliomas had homozygous p16/CDKN2A deletion in both the epithelioid and sarcomatoid components
  • In the biphasic mesotheliomas, p16/CDKN2A deletion status agreed 100% between the epithelioid and sarcomatoid components; the regression coefficient of determination was R2 = 0.6685
  • Including the 10 additional biphasic cases, 28 of 29 biphasic mesotheliomas (96.6%) had homozygous p16/CDKN2A deletion
  • 7 (77.8%) of 9 epithelioid mesotheliomas had homozygous p16/CDKN2A deletion; the fibrous stroma was analyzed in 7 of these cases and none had the deletion
  • 5 of 13 (38.5%) biphasic mesotheliomas were negative for BAP1. In 4 of these, both components were negative; in 1, the sarcomatoid component could not be analyzed.
  • 5 of 9 (55.6%) epithelioid mesotheliomas with atypical fibrosis were negative for BAP1, but the atypical fibrous stroma was BAP1-positive in all of them
• The authors' conclusion: The authors concluded that p16/CDKN2A FISH and BAP1 immunohistochemistry are helpful for distinguishing biphasic mesothelioma from epithelioid mesothelioma with reactive fibrosis
• Limitations the authors state:
  • The FISH probe spans about 222 kb, so smaller deletions of p16/CDKN2A cannot be detected or are only partly detected

Topics

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

Medical terms in this study, explained in our Lexicon: CDKN2A, Fluorescence In Situ Hybridization (FISH), BAP1, Immunohistochemistry, Biphasic Mesothelioma, Malignant Mesothelioma, Neoplasm, Histological Subtype.

Related studies

• BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma — S.M. McGregor, J. McElherne, et al. (2017)
• 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)
• MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)
• Utility of Methylthioadenosine Phosphorylase Compared With BAP1 Immunohistochemistry, and CDKN2A and NF2 Fluorescence In Situ Hybridization in Separating Reactive Mesothelial Proliferations From Epithelioid Malignant Mesotheliomas — K.B. Berg, S. Dacic, et al. (2018)
• 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)
• CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma — M. Betti, A. Aspesi, et al. (2016)

Browse more research in Annals of Diagnostic Pathology, or return to medical research.