Brca1-Associated Protein 1 (BAP1) Immunohistochemical Expression as a Diagnostic Tool in Malignant Pleural Mesothelioma Classification: a Large Retrospective Study

Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 2016 July 12 [Epub ahead of print] [Link]

Righi L, Duregon E, Vatrano S, Izzo S, Giorcelli J, Rondón-Lagos M, Ascoli V, Ruffini E, Ventura L, Volante M, Papotti M, Scagliotti GV


Malignant pleural mesothelioma (MPM) is a highly aggressive disease with limited therapeutic options. Histology remains among the most reliable prognostic factors, since epithelioid is associated with the best and sarcomatoid subtype with the worst prognosis. Biphasic subtype has an intermediate prognosis, but its definitive histological diagnosis may be challenging due to the difficult assessment of the neoplastic nature of the stromal component. Recent data identified BRCA1-Associated Protein 1 (BAP1) as one of the most frequently mutated genes in MPM. Immunohistochemistry for BAP1 has been proposed to be predictive for the detection of BAP1 mutation in neoplastic cells. The aim of the present study was to define the diagnostic usefulness of BAP1 immunohistochemical determination in MPM, with clinical-pathological correlation.
A series of 143 MPMs was investigated for BAP1 protein expression in correlation with clinical and pathological data, including a newly proposed nuclear grade. A pilot series of twenty selected cases were also investigated for BAP1 mutational status.
Nuclear negative staining for BAP1 occurred in 62% of MPMs (including 27% of cytoplasmic pattern) and was significantly associated with the presence of BAP1 mutation, epithelioid subtype and a better prognosis. In a subgroup of cases, the pattern of expression of BAP1 in stromal cells supported their distinction into reactive vs neoplastic, thus helping the correct classification of biphasic histology.
We showed that BAP1 protein determination is a diagnostic tool to correctly distinguish biphasic MPM from epithelial subtypes with an atypical/activated reactive stroma and is an independent prognostic parameter in MPM.