Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma

Our plain-English summary of Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma, by J. Andrici, J. Jung, A. Sheen, et al (Human Pathology, 2016).

The study

• Authors: J. Andrici, J. Jung, A. Sheen, L. D'Urso, L. Sioson, J. Pickett, T.R. Parkhill, B. Verdonk, K.L. Wardell, A. Singh, A. Clarkson, N. Watson, C.W. Toon, A.J. Gill
• Journal: Human Pathology
• Published: 2016;51:9-15
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Gynecologic and primary peritoneal serous carcinoma may be difficult to distinguish from abdominal mesotheliomas clinically, morphologically, and immunohistochemically. BAP1 double-hit inactivation and subsequent loss of protein expression have been reported in more than half of all abdominal mesotheliomas. We therefore sought to investigate the expression of BAP1 in serous carcinoma and explore its potential utility as a marker in the differential diagnosis with mesothelioma. We searched the computerized database of the Department of Anatomical Pathology, Royal North Shore Hospital, Australia, for all cases of gynecologic and peritoneal serous carcinomas and mesotheliomas diagnosed between 1998 and 2014. Immunohistochemistry for BAP1 was then performed on tissue microarray sections. Cases with completely absent nuclear staining in the presence of a positive internal control in nonneoplastic cells were considered negative. If staining was equivocal (eg, absent nuclear staining but no internal control), staining was repeated on whole sections. Loss of BAP1 expression was found in only 1 of 395 (0.3%) serous carcinomas but in 6 of 9 (67%) abdominal mesotheliomas (P < .001) and 131 of 277 (47%) thoracic mesotheliomas (P < .001). We conclude that BAP1 loss occurs extremely infrequently in gynecologic and peritoneal serous adenocarcinomas, whereas it is very common in mesotheliomas including abdominal mesothelioma. Therefore, although positive staining for BAP1 cannot be used to exclude a diagnosis of mesothelioma, loss of BAP1 expression can be used to very strongly support a pathological diagnosis of abdominal mesothelioma over serous carcinoma.

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In plain English

This laboratory study from Royal North Shore Hospital in Sydney, Australia, asked whether a tissue stain for the BAP1 protein can help pathologists tell abdominal mesothelioma apart from serous carcinoma, a cancer of the ovary, fallopian tube, uterus or peritoneum that can look similar. The study did not examine asbestos exposure. The authors stained archived tumour samples from 395 patients with serous carcinoma, 9 with abdominal mesothelioma and 277 with thoracic mesothelioma. They counted a tumour as BAP1-negative only when the stain was completely absent in tumour cells while nearby normal cells still stained. BAP1 was missing in 1 of 395 serous carcinomas (0.25%), compared with 6 of 9 abdominal mesotheliomas (67%) and 131 of 277 thoracic mesotheliomas (47%). The authors reported these differences as statistically significant. The single negative serous carcinoma was a primary peritoneal tumour, and further testing confirmed it was serous carcinoma. The authors concluded that loss of BAP1 strongly supports a diagnosis of mesothelioma over serous carcinoma. They cautioned that normal BAP1 staining cannot rule out mesothelioma, and that negative results need internal controls to exclude technical failure.

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 laboratory (pathology) study of archived tumour cases, using immunohistochemical staining for BAP1 on tissue microarrays, with repeat staining on whole sections when results were unclear
• Who was studied: 395 patients with serous carcinoma of the ovary, fallopian tubes, uterus or peritoneum diagnosed June 1998 to December 2012, plus 9 abdominal and 277 thoracic mesothelioma patients diagnosed January 1991 to November 2015, at Royal North Shore Hospital, Sydney, Australia
• Exposure: No asbestos or fiber exposure was studied. The factor examined was the presence or loss of BAP1 protein staining (immunohistochemistry) in tumour tissue.
• Main results:
  • Among serous carcinoma patients, BAP1 staining was negative in 1 of 395 (0.25%)
  • Among abdominal mesothelioma patients, BAP1 loss was found in 6 of 9 (67%)
  • The difference between abdominal mesotheliomas (67%) and serous carcinomas (0.25%) was reported as highly significant (p less than 0.001)
  • Among thoracic mesothelioma patients, BAP1 loss was found in 131 of 277 (47%)
  • The single BAP1-negative serous carcinoma was a primary peritoneal high grade serous carcinoma. Further staining confirmed it was serous carcinoma and not mesothelioma.
  • BAP1 staining was equivocal on tissue microarray sections in 7 serous carcinomas, which were restained on whole sections
• The authors' conclusion: The authors concluded that, when the differential diagnosis is mesothelioma versus serous carcinoma, loss of BAP1 expression can be used to strongly and virtually definitively make the diagnosis of mesothelioma, but positive BAP1 staining cannot exclude mesothelioma.
• Limitations the authors state:
  • About one third of abdominal and half of thoracic mesotheliomas kept BAP1 staining, so positive staining cannot rule out mesothelioma
  • A negative result must be distinguished from technical staining failure, so positive staining in normal cells (an internal control) is required before calling a case negative

Topics

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

Medical terms in this study, explained in our Lexicon: BAP1, Adenocarcinoma, Differential Diagnosis, Mesothelioma, Carcinoma, Pathology, Immunohistochemistry.

Related studies

• Loss of expression of BAP1 is very rare in non-small cell lung carcinoma — J. Andrici, T.R. Parkhill, et al. (2016)
• Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology — J. Andrici, A. Sheen, et al. (2015)
• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)
• Loss of expression of BAP1 predicts longer survival in mesothelioma — M. Farzin, C.W. Toon, et al. (2015)
• Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer — D. Owen, B.S. Sheffield, et al. (2017)
• Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions — I. Cozzi, F.A. Oprescu, et al. (2018)

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