BAP1 protein is a progression factor in malignant pleural mesothelioma

Our plain-English summary of BAP1 protein is a progression factor in malignant pleural mesothelioma, by L. Arzt, F. Quehenberger, I. Halbwedl, et al (Pathology Oncology Research, 2014).

The study

• Authors: L. Arzt, F. Quehenberger, I. Halbwedl, T. Mairinger, H.H. Popper
• Journal: Pathology Oncology Research
• Published: 2014;20(1):145-51
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma. Our study aimed to clarify if asbestos exposure has an influence on BAP1 expression and if BAP1 expression could be used as a prognostic factor of outcome. An immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and the expression levels have been correlated with asbestos exposure and overall survival time. BAP1 expression was not associated with asbestos exposure but we detected a significant effect of BAP1 expression on overall survival time--the higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival. BAP1 mutation has been linked to non-asbestos induced familial mesotheliomas, which usually belong to the long survivor group and BAP1 is most probably functioning differently than in sporadic cases. Further investigations need to be performed to characterize the BAP1 mutations and to identify the BAP1 downstream targets in MPM.

In plain English

Researchers at the Medical University of Graz, Austria, examined tumor tissue from 123 patients with malignant mesothelioma, all of whom had surgery. Of these samples, 66 came from Graz and 57 from Berlin. They stained the samples for BAP1, a tumor suppressor protein, and scored how strongly and how widely it appeared. Sixty percent of cases showed no BAP1 staining. Asbestos exposure information was available for 52 patients, 21 of whom had a history of asbestos exposure. In these 52 patients, exposure had no statistically significant effect on BAP1 levels (p = 0.93). The article gave no fiber types or exposure details. Across all 123 patients, BAP1 score was significantly linked with overall survival (p = 0.0014). It was the only significant factor when age, sex and tumor subtype were analyzed together (p = 0.013). The results text reported that higher BAP1 expression went with shorter survival, but one figure caption states the opposite. The authors concluded that BAP1 expression was not associated with asbestos exposure but was associated with survival. They noted that whether absent staining reflects real BAP1 mutations remains unconfirmed.

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 study of archived tumor tissue: BAP1 immunohistochemistry on tissue microarrays, compared with asbestos exposure history and overall survival (Kaplan-Meier and Cox regression)
• Who was studied: 123 human malignant mesothelioma samples (66 from the Medical University of Graz, Austria, and 57 from Berlin, Germany). Survival data were available for all 123 patients and asbestos exposure data for 52. The group was 89 male and 34 female. Tumors were 108 epithelioid, 1 sarcomatoid and 14 biphasic. All 123 patients had an operation. The article calls these cases malignant pleural mesothelioma (MPM) elsewhere. No study years are given.
• Exposure: History of asbestos exposure, recorded only as exposed or not exposed (21 of 52 patients with exposure data had been exposed). No fiber types, jobs or doses were reported. BAP1 protein expression in the tumor was also studied as a possible predictor of survival.
• Main results:
  • 60% of the mesothelioma cases did not stain positively for BAP1.
  • Among the 52 patients with exposure data, asbestos exposure had no statistically significant effect on BAP1 expression (p = 0.93).
  • Overall survival did not differ significantly between the Graz and Berlin sample groups (p = 0.57), so the authors combined them.
  • In all 123 patients, BAP1 expression score had a significant effect on overall survival (p = 0.0014, score test of Cox regression).
  • Age, sex and tumor subtype were not significant. In the analysis that included these factors together, only BAP1 expression score was significant (p = 0.013).
  • When patients were split into two groups at a BAP1 score of 50, survival differed significantly (p = 0.048). The Results text states that higher BAP1 expression went with shorter overall survival. The Fig. 5 caption states the opposite.
• The authors' conclusion: The authors concluded that BAP1 expression was not associated with asbestos exposure. They took this to indicate that asbestos exposure is not responsible for BAP1 mutations or downregulation in this disease. They also concluded that higher BAP1 expression (non-mutated BAP1) was linked to shorter overall survival, and that further work is needed to characterize BAP1 mutations and BAP1's downstream targets.
• Limitations the authors state:
  • It was not established whether absent BAP1 staining reflects real BAP1 mutations or epigenetic downregulation.
  • Staining was assessed by only one pathologist; the results were checked with software.
  • The computer-based scoring could misclassify cells, sometimes counting stroma cells as tumor cells or missing tumor cells.

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, Pleural Mesothelioma, Asbestos Exposure, Tumor Suppressor Gene, Germline Mutation, Malignant Mesothelioma, Immunohistochemistry, Overall Survival.

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• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)
• Functional differences between wild-type and mutant-type BRCA1-associated protein 1 tumor suppressor against malignant mesothelioma cells — S. Hakiri, H. Osada, et al. (2015)
• 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)

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