Diagnostic accuracy of BRCA1-associated protein 1 in malignant mesothelioma: a meta-analysis

Our plain-English summary of Diagnostic accuracy of BRCA1-associated protein 1 in malignant mesothelioma: a meta-analysis, by L.M. Wang, Z.W. Shi, J.L. Wang, et al (Oncotarget, 2017).

The study

• Authors: L.M. Wang, Z.W. Shi, J.L. Wang, Z. Lv, F.B. Du, Q.B. Yang, Y. Wang
• Journal: Oncotarget
• Published: 2017;8(40):68863-68872
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Conventional measurements are not always helpful in the diagnosis of malignant mesothelioma (MM). Increasing studies indicate that loss of BRCA1-associated protein 1 (BAP1) detected by immunohistochemistry (IHC) is a useful diagnostic marker for MM. In this meta-analysis, we investigated the diagnostic accuracy of BAP1 in MM.

Results: In total, 12 eligible studies with a total of 1824 patients were selected. Results indicated that loss of BAP1 sustained a pooled sensitivity of 0.56 (95% CI, 0.50-0.62), specificity of 1.00 (95% CI, 0.95-1.00), PLR of 548.82 (95% CI, 11.31-2.7 × 104), NLR of 0.44 (95% CI, 0.39-0.50), DOR of 1247.78 (95% CI, 25.08 -6.2 × 104) in discriminating MM from non-MM. The AUC of 0.72, reflecting the SROC, indicated moderate diagnostic accuracy. Subgroup analysis showed that BAP1 detection in histological specimens owned the higher diagnostic performance than cytological ones. In addition, BAP1 showed superior diagnostic accuracy in epithelioid MM than biphasic or sarcomatoid MM.

Materials And Methods: PubMed, Embase and the Cochrane Library and reference lists of related articles were searched, and studies that evaluated the utility of BAP1 in MM were included. Data from eligible studies were pooled to estimate sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR). Summary receiver operating curves (SROC) was applied to estimate overall diagnostic accuracy.

Conclusions: Current meta-analysis indicates that detection of BAP1 by IHC is a useful diagnostic marker for MM. Loss of BAP1 almost provides confirming diagnosis for MM, while positive staining for BAP1 is not enough to exclude non-MM.

In plain English

This systematic review and meta-analysis pooled 12 retrospective studies published between 2015 and 2017. They tested whether loss of the protein BAP1 on immunohistochemical staining helps distinguish malignant mesothelioma from other conditions such as non-small cell lung cancer. The studies covered 1824 patients: 1016 with confirmed mesothelioma and 808 without. Asbestos exposure was not examined. Pooled sensitivity was 0.56 (95% CI 0.50 to 0.62) and specificity 1.00 (95% CI 0.95 to 1.00). BAP1 loss was seen in just over half of mesothelioma cases and rarely in comparison cases. The area under the curve was 0.72 (95% CI 0.68 to 0.76), which the authors rated as moderate accuracy. Tissue (histological) samples performed better than fluid (cytological) samples on some measures. In five studies, sensitivity was 0.74 (95% CI 0.66 to 0.80) in epithelioid, 0.50 (0.38 to 0.62) in biphasic and 0.07 (0.00 to 0.72) in sarcomatoid mesothelioma. The authors concluded that BAP1 staining is a valid but imperfect marker that should be combined with other markers. They reported high between-study variation and publication bias, and said small studies may overstate accuracy.

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: Systematic review and meta-analysis of diagnostic accuracy studies. All 12 included studies were retrospective.
• Who was studied: 12 studies published 2015 to 2017, found by searching PubMed, Embase and the Cochrane Library up to April 2017. They covered 1824 patients: 1016 with confirmed malignant mesothelioma and 808 without. The comparison group included non-small cell lung cancer, reactive mesothelial hyperplasia, benign mesothelioma, fibrous pleurisy and others.
• Exposure: Not an exposure study. The test examined was loss of BAP1 protein detected by immunohistochemistry (IHC) in histological (tissue) or cytological samples. Asbestos and fiber types were not studied.
• Main results:
  • All 12 studies pooled: sensitivity 0.56 (95% CI 0.50 to 0.62) and specificity 1.00 (95% CI 0.95 to 1.00) for BAP1 loss in diagnosing mesothelioma.
  • Overall area under the summary ROC curve was 0.72 (95% CI 0.68 to 0.76), which the authors described as moderate diagnostic accuracy.
  • Heterogeneity between studies was high: I-squared 87.00% (95% CI 73.38 to 100.00).
  • The Egger's test indicated publication bias (p = 0.001).
  • Sensitivity and specificity did not differ significantly between cytological specimens (5 studies) and histological specimens (10 studies). On diagnostic odds ratio and AUC, histological specimens performed better: AUC 0.75 and DOR 423.81 for histology, against AUC 0.69 and DOR 53.47 for cytology.
  • In 5 studies with subtype data, epithelioid mesothelioma had sensitivity 0.74 (95% CI 0.66 to 0.80), specificity 1.00 (95% CI 0.53 to 1.00) and AUC 0.79. Biphasic mesothelioma had sensitivity 0.50 (95% CI 0.38 to 0.62), specificity 1.00 (95% CI 0.45 to 1.00) and AUC 0.58.
  • For sarcomatoid mesothelioma, sensitivity was 0.07 (95% CI 0.00 to 0.72), specificity 1.00 (95% CI 0.49 to 1.00) and AUC 0.86. The authors said the low sensitivity limits BAP1's usefulness for this subtype.
• The authors' conclusion: The authors concluded that BAP1 detection by IHC is a valid but imperfect diagnostic marker for malignant mesothelioma. They said loss of BAP1 almost rules in mesothelioma, and that BAP1 needs to be combined with other markers, such as p16, to improve sensitivity.
• Limitations the authors state:
  • Studies published only as abstracts or letters were excluded, which may cause publication bias. Obvious publication bias was observed and may distort the conclusions.
  • The number of included studies was small, especially in the subgroups. Some studies had few subjects, which may overestimate true diagnostic accuracy.
  • A random-effects model was used because of significant heterogeneity, which might have affected the results.
  • The pooled estimates must be interpreted with caution because of high heterogeneity and bias.
  • The better accuracy found for epithelioid mesothelioma may reflect how common that subtype is, which may cause diagnostic bias.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Meta-Analysis, BAP1, Immunohistochemistry, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Odds Ratio.

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• Diagnostic accuracy of circulating miR-126 for malignant pleural mesothelioma: a systematic review and meta-analysis — L. Zhang, Q. Zhou, et al. (2021)
• BRCA1-Associated Protein 1 (BAP1) Immunohistochemical Expression as a Diagnostic Tool in Malignant Pleural Mesothelioma Classification: A Large Retrospective Study — L. Righi, E. Duregon, et al. (2016)
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