Sarcomatoid Mesothelioma: A CDKN2A molecular analysis of 53 cases with immunohistochemical correlation with BAP1

Our plain-English summary of Sarcomatoid Mesothelioma: A CDKN2A molecular analysis of 53 cases with immunohistochemical correlation with BAP1, by M. Zaleski, N. Kalhor, J. Fujimoto, et al (Pathology, Research and Practice, 2020).

The study

• Authors: M. Zaleski, N. Kalhor, J. Fujimoto, I. Wistuba, C.A. Moran
• Journal: Pathology, Research and Practice
• Published: 2020;216(12):153267
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Fifty-three cases of sarcomatoid pleural mesothelioma were evaluated for CDKN2A (p16) homozygous deletion and correlated with BRCA-associated protein-1 (BAP1) expression by immunohistochemistry. The patients are 45 men and 8 women between the ages of 37 and 79 years (average age: 58 years), who presented with symptoms of chest pain, cough, and weight loss. Diagnostic imaging showed the presence of diffuse pleural thickening with encasement of the lung parenchyma in all the cases. All patients were surgically treated with extrapleural pneumonectomy. Loss of BAP1 reactivity was seen in 49 tumors and p16 homozygous deletion was seen in 41 tumors, while in 16 patients either BAP1 or p16 were noncontributory to the diagnosis of mesothelioma. However, we were able to detect a better survival rate in those patients in whom BAP1 was lost and p16 showed homozygous deletion. Our findings showed that even though the use of BAP1 and p16 are important tools in the diagnosis of mesothelioma, a proportion of cases still remains negative with approximately 30 % of the cases in which the concordance of BAP1 loss and p16 homozygous deletion will not be present. We consider that the final diagnosis of mesothelioma is best accomplished by a global interpretation of clinical, radiographic, and pathological features including immunohistochemistry and molecular studies.

Copyright © 2020. Published by Elsevier GmbH.

In plain English

This study looked back at 53 patients (45 men, 8 women, aged 37 to 79) at MD Anderson Cancer Center in Texas who had extrapleural pneumonectomy for sarcomatoid pleural mesothelioma between 1996 and 2015. The article did not report on asbestos exposure. The authors tested the tumors for two diagnostic markers: loss of the BAP1 protein and homozygous deletion of the CDKN2A (p16) gene. BAP1 loss was seen in 49 of 53 tumors (92%). Using the laboratory's own 2.7% cut-off, p16 deletion was found in 41 of 53 (77%). With the commonly used 10% cut-off, it was found in 33 of 53 (62%). The article reports 40 tumors (75%) with both changes and one with neither, but these counts do not agree with each other. All 53 patients died of disease. Median survival, measured from surgery, was 0.5 years. Neither marker alone was linked to a statistically significant survival difference. Patients with both changes lived longer on average (14 versus 10 months, p = 0.039). The authors concluded that diagnosis is best made by weighing clinical, imaging and pathology findings together, and they called for larger studies of the survival finding.

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: Retrospective case series from a single hospital's surgical pathology files, with laboratory testing of the tumors (BAP1 immunohistochemistry and p16 FISH) and survival analysis
• Who was studied: 53 patients (45 male, 8 female, aged 37 to 79, average 58) with sarcomatoid pleural mesothelioma treated by extrapleural pneumonectomy at The University of Texas MD Anderson Cancer Center, Houston, 1996 to 2015
• Main results:
  • BAP1 loss was found in 49 of 53 tumors (92%). BAP1 was retained in 4.
  • Using the in-house cut-off of 2.7%, p16 homozygous deletion was found in 41 of 53 tumors (77%).
  • Using the commonly used 10% cut-off, p16 homozygous deletion was found in 33 of 53 tumors (62%). Using a 20% cut-off, it was found in 26 of 53 (reported as 49% in the text).
  • The article reports 40 tumors (75%) with both BAP1 loss and p16 homozygous deletion. These counts do not agree with each other or with the article's other figures, as explained under text problems.
  • The article also reports that, of the 12 tumors without p16 homozygous deletion, 11 had BAP1 loss, so 1 tumor showed neither change. These counts do not agree with each other or with the article's other figures, as explained under text problems.
  • All 53 patients died of disease. Survival was measured from the date of surgery to death. It ranged from 0.5 to 3 years, with a median of 0.5 years.
  • There was no statistically significant survival difference by p16 deletion status alone, by BAP1 status alone, or by age above or below 60. Mean survival was 13.1 months with p16 deletion versus 9 months without. It was 12.7 months with BAP1 loss versus 10.6 months with BAP1 retained.
  • Patients whose tumors had both p16 homozygous deletion and BAP1 loss had a statistically significant longer survival than all other patients (p = 0.039). Mean survival was 14 months in this group versus 10 months in the rest.
• The authors' conclusion: The authors concluded that p16 FISH combined with BAP1 testing may aid the diagnosis of sarcomatoid mesothelioma, but that both markers can be negative in a small subset of cases. They considered the best practice to be an overall interpretation of clinical, radiological, histological, immunohistochemical and molecular findings.
• Limitations the authors state:
  • The authors stated that larger studies are needed to determine whether the combination of p16 deletion and BAP1 loss is linked to better survival.
  • The authors stated that a more universal approach to the p16 deletion cut-off is needed to properly judge the test's accuracy, since detection rates depend on the cut-off used.

Topics

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

Medical terms in this study, explained in our Lexicon: Sarcomatoid, Mesothelioma, CDKN2A, BAP1, Pleural Mesothelioma, Homozygous Deletion, Immunohistochemistry, Diffuse Pleural Thickening.

Related studies

• 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)
• BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas — H.C. Hwang, S. Pyott, et al. (2016)
• 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)
• 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)
• Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma — R. Pillappa, J.J. Maleszewski, et al. (2018)
• 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)

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