Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens

Our plain-English summary of Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens, by K.B. Berg, A.M. Churg, S. Cheung, et al (Cancer Cytopathology, 2020).

The study

• Authors: K.B. Berg, A.M. Churg, S. Cheung, S. Dacic
• Journal: Cancer Cytopathology
• Published: 2020;128(2):126-132
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The separation of benign from malignant mesothelial proliferations on effusion cytology can be difficult. Loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry is an established marker of malignancy in mesothelial proliferations, but to the authors' knowledge largely has been applied only to biopsies. The current study was conducted to determine the usefulness of MTAP immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens.

Methods: A total of 21 effusion cytology cases of malignant mesothelioma were stained for MTAP and BRCA-associated protein 1 (BAP1), with 15 reactive mesothelial cytology cases used as a control. Fourteen cases had a paired surgical specimen for comparison, and 7 cases were run for CDKN2A deletion by fluorescence in situ hybridization.

Results: Complete loss of MTAP cytoplasmic staining was noted in 7 of 21 effusion samples (33%), and no loss was observed in 11 effusion samples (52%); 11 of these cases had a matching surgical specimen and all 11 specimens demonstrated the same MTAP pattern. Partial loss was observed in 3 effusion specimens (80%, 40%, and 40% intact staining, respectively), but in all 3 the surgical specimen demonstrated 100% staining. None of the 15 reactive mesothelial cytology specimens demonstrated MTAP cytoplasmic loss. CDKN2A FISH demonstrated concordance in 5 of 7 cases (71%). MTAP immunohistochemistry had a sensitivity of 33% and a specificity of 100% for this differential diagnosis.

Conclusions: MTAP staining demonstrated generally good concordance between the cytologic and surgical specimens and appears to be useful in the diagnosis of mesothelioma on effusion specimens. Complete loss of MTAP is a reliable marker of malignancy, but the significance of partial loss of MTAP staining is unclear.

© 2019 American Cancer Society.

In plain English

This retrospective study, using cases from Vancouver General Hospital in Canada and the University of Pittsburgh Medical Center, asked whether a laboratory stain for a protein called MTAP helps tell malignant mesothelioma apart from harmless (reactive) mesothelial cells in fluid drawn from the chest. The authors examined 21 usable fluid samples from people with malignant pleural mesothelioma, collected between 2014 and 2018, and 15 reactive samples for comparison. They also stained for a second protein, BAP1. Complete loss of MTAP staining appeared in 7 of 21 mesothelioma samples (33%) and in none of the reactive samples, a sensitivity of 33% and a specificity of 100%. Three mesothelioma samples showed partial loss, but their matching surgical biopsies stained normally. Loss of either MTAP or BAP1 was seen in 15 of 21 mesothelioma samples (71%). The authors concluded that complete MTAP loss can safely be read as malignant, but that a normal result does not mean the process is benign. The article does not discuss 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: Small retrospective diagnostic study (laboratory staining of stored cytology samples, with a control group)
• Who was studied: 24 malignant pleural mesothelioma effusion (pleural fluid) cytology cases from 2014 to 2018: 11 from the University of Pittsburgh Medical Center and 13 from Vancouver General Hospital. 3 were excluded, leaving 21. 14 had a paired surgical biopsy. There were also 15 reactive mesothelial cytology cases from the same period as controls.
• Exposure: No asbestos or fiber exposure is reported. The study evaluated laboratory tests: MTAP and BAP1 immunohistochemistry on cell blocks, with CDKN2A FISH on some surgical specimens.
• Main results:
  • In the mesothelioma effusion samples, 7 of 21 (33%) showed complete loss of MTAP cytoplasmic staining.
  • None of the 15 reactive control samples lost MTAP staining. MTAP staining had a sensitivity of 33% and a specificity of 100% for distinguishing mesothelioma from reactive cells in cytology. The Fisher exact test comparing the 21 mesothelioma and 15 reactive cases was statistically significant (P = .03).
  • Of the cases with a matching surgical specimen, all 11 with complete loss or no loss showed the same MTAP pattern in cytology and surgery.
  • Three cytology specimens showed partial MTAP loss (80%, 40% and 40% staining). Their 3 surgical specimens showed no loss. Partial cases were counted as intact.
  • BAP1 loss was seen in 12 of 19 interpretable mesothelioma cytology cases (63%). Loss of either MTAP or BAP1 was seen in 15 of 21 mesothelioma cytology cases (71%).
  • MTAP staining and CDKN2A FISH agreed in 5 of 7 interpretable paired cases (71%).
  • Complete nuclear MTAP loss did not differ significantly between the 21 mesothelioma and 15 reactive cases.
• The authors' conclusion: The authors concluded that effusion cases in which all malignant cells have lost MTAP staining can be diagnosed safely as malignant. They said cases with less than complete loss should be called 'intact' or 'indeterminate'. They added that combining MTAP with BAP1 increases sensitivity.
• Limitations the authors state:
  • The authors describe the cohort as small and retrospective.
  • The authors state that both markers have limited sensitivity, and that failing to find MTAP or BAP1 loss does not mean the process is benign.
  • The authors say partial MTAP loss in effusions calls for caution in interpretation.
  • The authors state that the combined MTAP and BAP1 sensitivity in effusions was lower than in tissue.

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

Related studies

• 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)
• 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)
• 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 — W. Althakfi, S. Gazzo, et al. (2020)
• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)
• Correlation of methylthioadenosine phosphorylase (MTAP) protein expression with MTAP and CDKN2A copy number in malignant pleural mesothelioma — D.B. Chapel, A.M. Dubuc, et al. (2021)
• BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas — H.C. Hwang, S. Pyott, et al. (2016)

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