Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy

Our plain-English summary of Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy, by P. Boffetta, L. Righi, C. Ciocan, et al (Annals of Oncology, 2018).

The study

• Authors: P. Boffetta, L. Righi, C. Ciocan, C. Pelucchi, C. La Vecchia, C. Romano, M. Papotti, E. Pira
• Journal: Annals of Oncology
• Published: 2018;29(2):484-489
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Diagnosis of mesothelioma based on death certificate is subject to misclassification, which may bias the results of epidemiology studies. A high proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1 (BAP1) gene.

Methods: We searched medical and pathology records and specimens for 127 workers from a textile-asbestos factory in Italy who died during 1963-2013 with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death certificate, to confirm the diagnosis with immunohistochemistry markers. We calculated the odds ratio of confirmation by selected characteristics and asbestos exposure variables. When sufficient pathology material was available, we analyzed BAP1 protein expression.

Results: The diagnosis of mesothelioma was histologically confirmed for 35 cases (27.6%); 5 cases were classified as non-mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record but no sufficient material was available for revision (26.0%); no records were available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation was not associated with sex, location of the neoplasm, age, or duration of employment; however, there was a significant association with time since first employment (P for linear trend 0.04). An association between duration of employment and time since first employment was observed for confirmed cases but not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases (51.4%), without an association with sex, location, age, indices of asbestos exposure, or survival.

Conclusions: We were able to confirm by immunohistochemistry a small proportion of mesothelioma diagnoses on certificates of deceased asbestos workers, and confirmation correlated with latency of asbestos exposure but not other characteristics. BAP1 protein loss is a frequent event in mesothelioma of asbestos-exposed workers, but does not correlate with exposure.

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

In plain English

The authors checked death certificates of 127 asbestos textile workers near Turin, Northern Italy, who died between 1963 and 2013 with pleural or peritoneal cancer or mesothelioma recorded. The factory used mainly chrysotile, but also crocidolite. They searched hospital, pathology and registry records and re-examined tissue using immunohistochemistry. Mesothelioma was confirmed in 35 cases (27.6%). Another 5 (3.9%) were classified as non-mesothelioma; 33 (26.0%) had a recorded mesothelioma diagnosis but no material to review. For 54 (42.5%) no records were found. After adjustment for other factors, confirmation was not associated with sex, tumor site, age or duration of employment, but was associated with time since first employment (P for linear trend 0.04). An unadjusted comparison confirmed proportionally more women's cases. Among the 35 confirmed cases, BAP1 protein was lost in 18 (51.4%), with no association with sex, site, age, exposure measures or survival. The authors concluded that only a small proportion of certificate diagnoses could be confirmed and that BAP1 loss was frequent but not correlated with exposure. They named the small number of reviewable cases as the main limitation.

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: Validation study of death-certificate diagnoses within an existing cohort of asbestos textile workers. It used medical and pathology records and immunohistochemistry review of archived specimens, and analyzed BAP1 protein expression in confirmed cases.
• Who was studied: 127 members of a cohort of 1083 women and 894 men who worked in an asbestos textile factory in the metropolitan area of Turin, Piedmont, Northern Italy, between 1946 and 1984. The 127 died between 1963 and 2013 with pleural or peritoneal cancer or mesothelioma on the death certificate.
• Exposure: Occupational asbestos exposure in an asbestos textile factory, mainly chrysotile with crocidolite also present. Exposure was measured through time since first employment, duration of employment and time since last employment. There were no individual exposure levels.
• Main results:
  • Of the 127 decedents, mesothelioma was confirmed by histology and immunohistochemistry in 35 (27.6%), and 5 (3.9%) were classified as non-mesothelioma.
  • Of the 5 non-mesothelioma cases, four were classified because the medical or pathology report gave a diagnosis other than mesothelioma.
  • The fifth non-mesothelioma case was classified on the basis of information from the regional mesothelioma registry. The article does not give that person's alternative diagnosis.
  • 33 of the 127 (26.0%) had a mention of mesothelioma on record but not enough material to review. For 54 (42.5%) no records were available (death-certificate-only).
  • No case could be confirmed among the 31 who died before 1993. After excluding cohort members who died before 2000, the proportion of confirmed cases rose to 44% (29/66).
  • In the unadjusted (univariate) analysis, the article reports that the proportion of IHC-confirmed cases was higher among women (30.9%) than among men (17.7%, P-value of difference 0.002). These percentages do not match the counts in Table 1.
  • In the multivariate (adjusted) analysis, diagnostic confirmation was not associated with sex, site of the neoplasm, age or duration of employment. It was significantly associated with time since first employment (P for linear trend 0.04).
  • The odds ratio of confirmation was 18.0 (95% CI 1.80 to 179) for cases 35.0 to 44.9 years since first exposure, compared with under 25.0 years.
  • The odds ratio of confirmation was 14.3 (95% CI 1.20 to 170) for cases 45 or more years since first exposure, compared with under 25.0 years.
  • In the mortality analysis, the association with time since first employment was present for IHC-confirmed mesothelioma but not for death-certificate-only mesothelioma. For IHC-confirmed cases, the mortality rate ratio was 4.24 (95% CI 1.45 to 12.39) at 30 to 44 years since first employment, compared with under 30 years.
  • The P for trend by time since first employment was 0.03 for IHC-confirmed, 0.42 for record-based and 0.93 for death-certificate-only mesothelioma.
  • 76 of the 127 cases were listed in the Piedmont Regional Mesothelioma Registry. Taking this study's validation as the gold standard, the Registry's 'certain' classification had a sensitivity of 83% and a specificity of 34%.
  • Among the 35 confirmed cases, 18 (51.4%) had lost nuclear BAP1 protein expression.
  • BAP1 protein loss was not associated with sex, location, age, indices of asbestos exposure, or survival.
  • Survival did not differ by BAP1 status (Kaplan–Meier P = 0.30). The adjusted hazard ratio for negative BAP1 expression was 1.76 (95% CI 0.72 to 4.32).
• The authors' conclusion: The authors concluded that they could confirm by immunohistochemistry only a small proportion of mesothelioma diagnoses on the death certificates of deceased asbestos workers, and that confirmation correlated with latency of asbestos exposure but not with other characteristics. They also concluded that BAP1 protein loss is frequent in mesothelioma of asbestos-exposed workers but does not correlate with exposure.
• Limitations the authors state:
  • The main limitation was the small number of cases with enough material to confirm or disprove the diagnosis and to carry out the BAP1 analysis.
  • There were no individual data on level of asbestos exposure; proxy indicators such as duration of exposure were used instead.
  • The BAP1 analysis was hampered by the small number of cases with archival material, so the authors advised caution in interpreting it.
  • The finding of no survival difference by BAP1 status conflicts with earlier studies. The authors said this may be due to the small number of cases.
  • The cohort's time period and location make it difficult to generalize the results to other populations.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, BAP1, Death Certificate, Epidemiology, Pathology, Neoplasm, Immunohistochemistry, Odds Ratio.

Related studies

• Comment on the paper 'Boffetta et al. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy. Ann Oncol 2018; 29(2): 484-489' — D. Consonni, C. Mensi (2019)
• Comment on 'Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy' — C. Brentisci, M. Gangemi, et al. (2018)
• BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas — N. Leblay, F. Leprêtre, et al. (2017)
• 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)
• Mortality of Talc Miners and Millers From Val Chisone, Northern Italy: An Updated Cohort Study — E. Pira, M. Coggiola, et al. (2017)
• Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma — J. Andrici, J. Jung, et al. (2016)

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