A combination of MTAP and BAP1 immunohistochemistry is effective for distinguishing sarcomatoid mesothelioma from fibrous pleuritis

Our plain-English summary of A combination of MTAP and BAP1 immunohistochemistry is effective for distinguishing sarcomatoid mesothelioma from fibrous pleuritis, by Y. Kinoshita, M. Hamasaki, M. Yoshimura, et al (Lung Cancer, 2018).

The study

• Authors: Y. Kinoshita, M. Hamasaki, M. Yoshimura, S. Matsumoto, A. Sato, T. Tsujimura, H. Ueda, S. Makihata, F. Kato, A. Iwasaki, K. Nabeshima
• Journal: Lung Cancer
• Published: 2018;125:198-204
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Histologic diagnosis of malignant pleural mesothelioma (MPM) is not always straightforward. Loss of BRCA1-associated protein 1 (BAP1) expression as detected by immunohistochemistry (IHC) (BAP1 IHC) and homozygous deletion (HD) of 9p21 as detected by fluorescencein situ hybridization (FISH) (9p21 FISH) are effective for distinguishing malignant mesothelial proliferation from benign proliferation. We have previously reported that immunohistochemical expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, is correlated with the deletion status of 9p21 FISH in MPM tissues. In this study, we investigated whether a combination of MTAP and BAP1 IHC could distinguish sarcomatoid MPM from fibrous pleuritis.

Materials And Methods: We examined IHC expressions of MTAP and BAP1 and 9p21 FISH in sarcomatoid/desmoplastic (n = 18) and biphasic MPM (n = 12) and in fibrous pleuritis (n = 17). In biphasic MPM, only sarcomatoid components were evaluated for IHC and FISH. The sensitivity and specificity of each detection assay for discriminating MPM cases from fibrous pleuritis was determined. In addition, we compared the IHC expression of MTAP with the deletion status of 9p21 FISH.

Results: MTAP IHC and BAP1 IHC showed 80% and 36.7% sensitivity, respectively, and both showed 100% specificity in differentiating MPM from fibrous pleuritis. A combination of MTAP and BAP1 IHC yielded greater sensitivity (90%) than that detected for MTAP IHC alone or BAP1 IHC alone. Moreover, a high degree of concordance was observed between the results of MTAP IHC and HD of 9p21 FISH (κ = 0.63).

Conclusions: With an accurate interpretation of results, combined MTAP and BAP1 IHC is a reliable and effective method for distinguishing sarcomatoid MPM from fibrous pleuritis.

Copyright © 2018 Elsevier B.V. All rights reserved.

In plain English

This retrospective study from Fukuoka University Hospital in Japan tested whether two tissue staining tests (immunohistochemistry for the proteins MTAP and BAP1) could tell sarcomatoid malignant pleural mesothelioma apart from fibrous pleuritis, a non-cancerous condition that can be hard to distinguish from it. The authors examined 30 mesothelioma cases from 2001 to 2017: 18 sarcomatoid, including 8 desmoplastic, and 12 biphasic, in which only the sarcomatoid parts were assessed. They compared these with 17 fibrous pleuritis cases, 9 of which had a past history of asbestos exposure. Loss of MTAP staining was found in 80% of mesothelioma cases and loss of BAP1 staining in 36.7%. For each stain, neither loss was found in any of the 16 fibrous pleuritis cases that could be evaluated (100% specificity). Using both stains together identified 90% of mesothelioma cases. MTAP staining agreed well with a genetic test (FISH) for deletion of the 9p21 region, with a kappa of 0.63. Some samples could not be read. The authors concluded that, with accurate interpretation, the combination is a reliable and effective method for this distinction. They noted the study was single-center and small.

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: Single-center retrospective study of diagnostic test accuracy, using pathology specimens
• Who was studied: 30 malignant pleural mesothelioma cases with a sarcomatoid component (18 sarcomatoid, including 8 desmoplastic, and 12 biphasic; 27 males and 3 females, mean age 71.3) and 17 fibrous pleuritis cases (16 males and 1 female, mean age 69.2). All came from the pleural lesion files, including consultation cases, of the Department of Pathology, Fukuoka University Hospital, Japan, 2001 to 2017. Fibrous pleuritis was confirmed when there was no progression for at least a year; 5 of 22 such cases were excluded because they could not be followed for a year.
• Exposure: Asbestos exposure was not the focus of the study. The study evaluated diagnostic tests: MTAP immunohistochemistry, BAP1 immunohistochemistry, and 9p21 FISH. Of the 17 fibrous pleuritis cases, 9 had a past history of asbestos exposure. No fiber types are given.
• Main results:
  • In distinguishing the mesothelioma cases from fibrous pleuritis, MTAP immunohistochemistry had 100% specificity and 80% sensitivity. BAP1 immunohistochemistry had 100% specificity and 36.7% sensitivity.
  • The 100% specificity for each stain rested on the 16 fibrous pleuritis cases that could be evaluated. For each stain, one fibrous pleuritis case could not be interpreted, and none of the 16 evaluable cases showed loss.
  • Combining MTAP and BAP1 immunohistochemistry gave a sensitivity of 90% for the mesothelioma cases, higher than either test alone.
  • In the mesothelioma cases, loss of MTAP staining showed good agreement with 9p21 homozygous deletion detected by FISH (kappa coefficient 0.63).
  • In the mesothelioma cases, MTAP loss predicted 9p21 deletion detected by FISH with 100% specificity and 92.6% sensitivity (25 of 27 cases).
  • Some samples could not be interpreted: 2 of 47 samples (4.26%) for MTAP and 3 of 47 samples (6.38%) for BAP1.
• The authors' conclusion: The authors concluded that, with accurate interpretation of results, combined MTAP and BAP1 immunohistochemistry was a reliable and effective method for differentiating sarcomatoid malignant pleural mesothelioma from fibrous pleuritis. They also concluded that MTAP immunohistochemistry is a useful alternative when 9p21 FISH is not available.
• Limitations the authors state:
  • The study was a single-center retrospective study, and the number of patients was relatively small because the disease is rare. The authors stated that a larger prospective study is needed to confirm the results.
  • Interpreting MTAP and BAP1 staining can be difficult in some cases, and some samples could not be interpreted. The authors stated that such cases need 9p21 FISH or an additional biopsy.
  • The study included several old samples. The authors concluded that the time between sample collection and analysis did not influence the results.

Topics

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

Medical terms in this study, explained in our Lexicon: MTAP, BAP1, Immunohistochemistry, Sarcomatoid, Mesothelioma, Pleural Mesothelioma, Homozygous Deletion, Fluorescence In Situ Hybridization (FISH).

Related studies

• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)
• Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis — D. Wu, K. Hiroshima, et al. (2013)
• BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests — T. Hida, M. Hamasaki, et al. (2016)
• How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study — A.N. Husain, M.K. Mirza, et al. (2014)
• 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)
• Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry — T. Hida, M. Hamasaki, et al. (2017)

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