Can BAP1 expression loss in mesothelial cells be an indicator of malignancy?

Our plain-English summary of Can BAP1 expression loss in mesothelial cells be an indicator of malignancy?, by H.G. Ozdemir, S.C. Kokten, N.O. Barisik (Journal of Pathology and Translational Medicine, 2020).

The study

• Authors: H.G. Ozdemir, S.C. Kokten, N.O. Barisik
• Journal: Journal of Pathology and Translational Medicine
• Published: 2020;54(6):497-503
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma is a highly aggressive tumor that can be confused with a benign mesothelial lesion, especially cytomorphologic lesions. BRCA1-associated protein 1 (BAP1) acts as a tumor suppressor. In this study, we aim to investigate the value of BAP1 staining of malignant mesothelioma cases with expression loss and diagnosis in cell block and biopsy tissue.

Methods: Between January 2009 and March 2017, 64 mesotheliomas, 117 reactive mesothelial hyperplasias, and 20 fibrinous pleuritis/pericarditis were diagnosed with morphologic and immunohistochemical findings in our pathology clinic and were included in the study. Formalin-fixed, paraffin-embedded tissues were immunohistochemically examined for BAP1. Inflammatory and stromal cells were used as positive internal controls. BAP1 was assessed for nuclear staining in mesothelial cells.

Results: Examinations of the relationship between patient diagnosis and BAP1 biopsy status showed that the BAP1 loss rate (76.6%) was significantly higher in malignant mesothelioma cases than in other benign diseases (0%) (p<.001). Sensitivity and specificity were 76.56% and 100%, respectively, for biopsy tissue from malignant mesothelioma. Sensitivity and specificity were both 100% for BAP1 test on cell block tissue. Furthermore, the consistency between BAP1 cell block and biopsy results was excellent (ĸ=0.90) and the correlation was significant (p<.001).

Conclusions: This study shows that BAP1 expression loss in both cytology and biopsy tissue in biopsy-confirmed malignant mesothelioma cases is an essential parameter for malignant mesothelioma diagnosis.

In plain English

This retrospective study from Turkey tested whether loss of a protein called BAP1, detected by immunohistochemical staining, helps distinguish malignant mesothelioma from non-cancerous mesothelial conditions. The authors stained archived samples from 64 mesothelioma, 117 reactive mesothelial hyperplasia and 20 fibrinous pleuritis/pericarditis cases diagnosed between January 2009 and March 2017. In biopsy tissue, BAP1 loss was found in 49 of 64 mesotheliomas (76.6%) and none of the non-cancerous cases. Loss was found in 81.5% of epithelioid-type mesotheliomas and in none of the five sarcomatoid-type cases. Cell blocks made from fluid samples were available for 11 mesotheliomas and 9 non-cancerous cases; only epithelioid mesotheliomas had enough cell-block material. In these, BAP1 loss was found in all 11 mesotheliomas and none of the others, and 10 of those 11 also showed loss in biopsy. Asbestos exposure was recorded in 35.9% of mesothelioma cases; BAP1 loss did not differ significantly by exposure. The authors concluded that BAP1 loss is a robust criterion for diagnosing mesothelioma from fluid samples. They noted that the retrospective design meant not all fluid samples could be obtained.

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 study of archived pathology cases, assessing the diagnostic value of BAP1 immunohistochemical staining. Two pathologists who did not know the diagnosis read the slides.
• Who was studied: 201 cases diagnosed at the authors' pathology clinic in Turkey between January 2009 and March 2017: 64 malignant mesotheliomas (57 pleural, 6 peritoneal, 1 pericardial; 54 epithelioid, 5 sarcomatoid, 5 biphasic), 117 reactive mesothelial hyperplasias and 20 fibrinous pleuritis/pericarditis cases.
• Exposure: The factor studied was BAP1 immunohistochemical staining of biopsy tissue and of cell blocks made from cytological (effusion) material. Asbestos exposure was recorded as a patient characteristic: it was detected in 35.9% of mesothelioma cases. Fiber types are not specified.
• Main results:
  • In biopsy tissue, BAP1 expression loss was seen in 76.6% (49 of 64) of malignant mesothelioma cases and in 0% of the benign cases (0 of 117 reactive mesothelial hyperplasia, 0 of 20 fibrinous pleuritis/pericarditis); p less than .001.
  • By mesothelioma subtype in biopsy tissue, BAP1 loss was seen in 81.5% (44 of 54) of epithelioid cases and in none of the 5 sarcomatoid cases.
  • BAP1 loss was seen in all five biphasic mesothelioma cases. In every one, the loss was found in the epithelioid component and not in the sarcomatoid component.
  • In biopsy tissue, the sensitivity of BAP1 loss for diagnosing malignant mesothelioma was 76.56% and the specificity was 100%.
  • Only epithelioid mesotheliomas had sufficient cell-block material. In cell blocks, BAP1 loss was seen in all 11 mesothelioma cases (all epithelioid) and in none of the 9 benign cases (8 reactive mesothelial hyperplasia, 1 fibrinous pleuritis/pericarditis). Sensitivity and specificity were both reported as 100%.
  • Agreement between cell block and biopsy: 10 of the 11 patients (90.9%) with BAP1 loss in cell block also showed loss in biopsy, and all 9 with normal expression in cell block also had normal expression in biopsy. The authors reported a kappa of 0.90 (p less than .001).
  • Among mesothelioma cases, BAP1 loss did not differ significantly by age, sex, asbestos exposure, additional cancer or location (all p greater than .05). Table 4 shows loss in 17 of 23 (73.9%) asbestos-exposed and 32 of 41 (78.0%) non-exposed cases, p = .708.
• The authors' conclusion: The authors concluded that BAP1 expression loss is a robust criterion for diagnosing malignant mesothelioma from cytological material. They suggested that patients with only serous effusion who show BAP1 loss in cell blocks need strict clinical follow-up.
• Limitations the authors state:
  • Because the study was retrospective, it was not possible to obtain cytological specimens for all of the biopsy cases stained for BAP1.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Mesothelial Cells, Mesothelioma, Cell Block, Biopsy, Reactive Mesothelial Hyperplasia, Pathology, Cytology.

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