A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma

Our plain-English summary of A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma, by Y. Kinoshita, T. Hida, M. Hamasaki, et al (Cancer Cytopathology, 2018).

The study

• Authors: Y. Kinoshita, T. Hida, M. Hamasaki, S. Matsumoto, A. Sato, T. Tsujimura, K. Kawahara, K. Hiroshima, Y. Oda, K. Nabeshima
• Journal: Cancer Cytopathology
• Published: 2018;126(1):54-63
• Cited by: 88 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues. In the current study, the authors investigated whether a combination of MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in cell blocks obtained from pleural effusions.

Methods: The authors examined IHC expression of MTAP and BAP1 in cell blocks obtained from pleural effusions of 45 cases of MPM and 21 cases of reactive mesothelial hyperplasia. Furthermore, IHC expression of MTAP was compared with the deletion status of 9p21 FISH.

Results: MTAP and BAP1 IHC differentiated MPM from RMC with 100% specificity for both and sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1 IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed between the results of MTAP IHC and 9p21 FISH in cell blocks.

Conclusions: A combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to be a reliable and useful method for differentiating MPM cells from RMC and can be used in the routine diagnosis of MPM. Cancer Cytopathol 2018;126:54-63. © 2017 American Cancer Society.

© 2017 American Cancer Society.

In plain English

This Japanese study tested whether two laboratory stains could tell malignant pleural mesothelioma apart from non-cancerous (reactive) lining cells in fluid that collects around the lungs (pleural effusions). The stains show loss of two proteins, MTAP and BAP1. The authors used stored samples from Fukuoka University Hospital, collected 2005 to 2016, from 45 people with mesothelioma and 21 people with non-cancerous effusions. No non-cancer sample showed loss of either protein. Among mesothelioma samples, MTAP loss was found in 42.2% and BAP1 loss in 60.0%. Using both stains together detected 77.8%, compared with 62.2% for a genetic test called 9p21 FISH alone. MTAP staining agreed well with the FISH test (kappa 0.61). In the 30 mesothelioma patients who also had tissue samples, fluid and tissue gave identical results for all three tests. The authors concluded the MTAP and BAP1 combination was reliable and useful when interpreted properly. They noted the small number of cases and that sarcomatoid mesothelioma was not included. The study did not examine 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: Diagnostic test study on archived pleural effusion cell blocks. It compared MTAP and BAP1 immunohistochemistry, and 9p21 FISH, between mesothelioma and non-cancerous cases.
• Who was studied: 45 cases of malignant pleural mesothelioma (34 men, 11 women; 42 epithelioid, 3 biphasic) and 21 non-neoplastic cases with reactive mesothelial hyperplasia (12 men, 9 women). The non-neoplastic cases had benign effusions from patients with lung cancer (14), pneumonia (3) or cardiovascular disease (4). These were the cases left after exclusions from 52 mesothelioma and 30 non-neoplastic cases initially examined. All came from Fukuoka University Hospital files, 2005 to 2016.
• Exposure: No asbestos exposure was studied. The study evaluated diagnostic tests: loss of MTAP and BAP1 protein by immunohistochemistry, with a 50% cutoff, and homozygous deletion of 9p21 by FISH, with a 10% cutoff.
• Main results:
  • In pleural effusion cell blocks, MTAP IHC and BAP1 IHC each had 100% specificity: none of the 21 reactive cases showed loss. Sensitivity in the 45 mesothelioma cases was 42.2% for MTAP and 60.0% for BAP1.
  • Combining MTAP and BAP1 IHC gave a sensitivity of 77.8% in the mesothelioma cases, with 100% specificity. This was higher than BAP1 IHC alone (60.0%) or 9p21 FISH alone (62.2%).
  • The combination of 9p21 FISH and BAP1 IHC had the highest sensitivity, 84.4%, in the mesothelioma cases.
  • Among mesothelioma cases, MTAP IHC agreed with 9p21 FISH with a kappa coefficient of 0.61. Of the 28 cases with 9p21 deletion by FISH, 19 (67.9%) showed MTAP loss. No case without the deletion showed MTAP loss (specificity 100%).
  • In the 30 mesothelioma cases with corresponding tissue specimens, cell blocks and tissue gave identical results for BAP1 IHC, MTAP IHC and 9p21 FISH.
• The authors' conclusion: The authors concluded that combining MTAP and BAP1 IHC in pleural effusion cell blocks was a reliable and useful method for differentiating mesothelioma cells from reactive mesothelial cells, when the results were interpreted properly and accurately.
• Limitations the authors state:
  • Only epithelioid and biphasic mesotheliomas were included. Sarcomatoid tumor cells rarely appear in pleural effusions.
  • 11 cases were excluded for insufficient mesothelial cells.
  • MTAP loss could not be assessed in a few cases (4.9%) because of weak and uneven staining.
  • The number of cases analyzed was relatively small.

Topics

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

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

Related studies

• A combination of MTAP and BAP1 immunohistochemistry is effective for distinguishing sarcomatoid mesothelioma from fibrous pleuritis — Y. Kinoshita, M. Hamasaki, 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)
• 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)
• 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)
• HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion — K. Hiroshima, D. Wu, et al. (2021)
• 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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