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

Our plain-English summary of 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, by K.B. Berg, S. Dacic, C. Miller, et al (Archives of Pathology & Laboratory Medicine, 2018).

The study

• Authors: K.B. Berg, S. Dacic, C. Miller, S. Cheung, A. Churg
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2018;142(12):1549-1553
• Cited by: 99 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context.—: The separation of reactive from malignant mesothelial proliferations is often a difficult morphologic problem. There is contradictory information in the literature on whether methylthioadenosine phosphorylase (MTAP) immunohistochemistry can be used for this purpose.

Objective.—: To determine the utility of MTAP immunohistochemistry in distinguishing reactive from malignant mesothelial proliferations.

Design.—: We stained a tissue microarray containing 20 epithelioid malignant mesotheliomas and 17 reactive mesothelial proliferations. For the mesotheliomas, comparisons were made between MTAP staining and BRCA-associated nuclear protein 1 (BAP1) immunohistochemistry, cyclin-dependent kinase inhibitor 2A ( CDKN2A) fluorescence in situ hybridization, and neurofibromin 2 ( NF2) fluorescence in situ hybridization, which are established techniques for making this separation.

Results.—: Loss of MTAP was seen in 0 of 17 reactive mesothelial proliferations and 13/20 (65%) malignant mesotheliomas. Almost all cases with loss showed loss in 100% of mesothelial cells. Background inflammatory and stromal cells served as a positive internal control. CDKN2A fluorescence in situ hybridization on the mesotheliomas showed concordance with MTAP staining in 14 of 17 evaluable cases. BAP1 immunohistochemistry showed loss of nuclear staining in 11 of 20 mesotheliomas (55%). No cases showed loss of NF2. A total of 18 of 20 mesotheliomas (90%) showed loss of either MTAP or BAP1.

Conclusions.—: In the context of a mesothelial proliferation, loss of MTAP staining is 100% specific for malignant mesothelioma. In this study the combination of MTAP and BAP1 immunohistochemical staining allowed separation of reactive from epithelial malignant mesothelial proliferations in 90% of cases.

In plain English

This laboratory study asked whether a tissue stain for the protein MTAP can help pathologists tell epithelioid malignant mesothelioma apart from benign (reactive) growths of mesothelial cells, the cells that line body cavities. The authors stained a tissue microarray of samples from 20 epithelioid malignant mesotheliomas (18 pleural, 2 peritoneal) and 17 reactive mesothelial proliferations. They compared the MTAP results with established tests: BAP1 staining, and CDKN2A and NF2 gene tests (FISH). None of the 17 reactive proliferations lost MTAP staining, while 13 of 20 mesotheliomas (65%) did. MTAP staining agreed with the CDKN2A gene test in 14 of the 17 mesotheliomas that could be tested. BAP1 staining was lost in 11 of 20 mesotheliomas (55%), and no tested case showed NF2 deletion. The article reports that 18 of 20 mesotheliomas (90%) lost either MTAP or BAP1. The authors concluded that, in a mesothelial proliferation, MTAP loss was 100% specific for malignant mesothelioma. The study did not look at asbestos exposure, and some counts differ between the article's text and tables.

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: immunohistochemical staining and fluorescence in situ hybridization (FISH) on a tissue microarray
• Who was studied: Tissue samples on one tissue microarray: 20 epithelioid malignant mesotheliomas (18 pleural, 2 peritoneal) and 17 reactive mesothelial proliferations, plus 12 high-grade serous ovarian carcinomas and 21 lung adenocarcinomas for comparison. Ethics approval came from the University of British Columbia, Vancouver, Canada. The article does not state where or when the cases were collected.
• Exposure: No asbestos or fiber exposure was studied. The study compared diagnostic tests: MTAP immunohistochemistry (antibody clone 2G4), BAP1 immunohistochemistry (clone C4), and CDKN2A and NF2 FISH.
• Main results:
  • None of the 17 reactive mesothelial proliferations showed loss of MTAP staining.
  • MTAP staining was lost in 13 of 20 epithelioid malignant mesotheliomas (65%).
  • Among the mesotheliomas, 11 lost MTAP in 100% of mesothelial cells. In 2 other cases loss was in 50% and 75% of cells, and these were counted as MTAP loss.
  • BAP1 staining was lost in none of the reactive proliferations and in 11 of 20 malignant epithelioid mesotheliomas (55%).
  • CDKN2A deletion by FISH was found in 12 of the 17 mesotheliomas that could be evaluated (printed as 60%).
  • MTAP staining and CDKN2A FISH agreed in 14 of 17 evaluable mesotheliomas (82%).
  • NF2 FISH showed no NF2 deletion in any of 17 evaluable mesotheliomas.
  • The article reports that 18 of 20 mesotheliomas (90%) showed loss of either MTAP or BAP1.
  • Among comparison tumors, lung adenocarcinomas had MTAP loss reported as 14% (4 of 21) and BAP1 loss in 0 of 21. High-grade ovarian serous carcinomas had MTAP loss in 1 of 12 (8%) and BAP1 loss in 0 of 12.
• The authors' conclusion: The authors concluded that, in the context of a mesothelial proliferation, loss of MTAP staining is 100% specific for malignant mesothelioma, and that in this study MTAP and BAP1 staining together separated reactive from epithelioid malignant proliferations in 90% of cases.

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: BAP1, Immunohistochemistry, CDKN2A, Fluorescence In Situ Hybridization (FISH), Epithelioid, Malignant Mesothelioma, MTAP, Mesothelioma.

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)
• 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)
• 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)
• 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)
• Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma — D. Wu, K. Hiroshima, et al. (2017)
• Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report — K. Minami, N. Jimbo, et al. (2020)

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