P3.03-013 BAP1 Immunostaining and FISH Analysis of p16 Help Making Distinction among Subtypes of Mesothelioma: Topic: Mesothelioma Transitional

Abstract

Distinction between mesothelioma and reactive mesothelial proliferation is difficult because of morphological overlap between mesothelioma cells and reactive mesothelial cells. It is often difficult to draw the line between epithelioid mesothelioma and biphasic mesothelioma with atypical stromal proliferation. However, separation of biphasic mesothelioma from epithelioid mesothelioma is important because therapeutic option and prognosis is different between two subtypes of mesothelioma. We collected 143 cases with malignant mesotheliomas (83 epithelioid, 22 biphasic and 38 sarcomatoid) and 33 cases with reactive mesothelial proliferation. Immunostaining was performed with anti-BAP1 antibody. Fluorescence in situ hybridization (FISH) analysis was performed with BAP1 probe and with p16 probe. BAP1 loss and deletion of p16 was separately analyzed in 19 biphasic mesotheliomas. We analyzed 76 cases with BAP1 immunostaining, 87 cases with p16 FISH, and 37 cases with BAP1 FISH. BAP1 loss with immunohistochemistry was observed in 55% of epithelioid and 37% of biphasic mesotheliomas, but not in sarcomatoid mesotheliomas. Homozygous deletion (HD) of BAP1 was observed in 50% of epithelioid and 11% of biphasic mesotheliomas, but not in sarcomatoid mesotheliomas. HD of p16 was observed in 64% of epithelioid, 91% of biphasic, and 100% of sarcomatoid mesotheliomas. Concordance of BAP1 loss and HD of p16 between epithelioid and sarcomatoid components of 19 biphasic mesotheliomas was 100%. Four of epithelioid mesotheliomas were difficult to differentiate from biphasic mesothelioma with histology alone because of florid proliferation of atypical stromal cells; however, BAP1 loss and HD of p16 were not observed in atypical stromal proliferation and diagnosis of epithelioid mesothelioma could be made. There was a significant difference in overall survival according to histologic subtype (epithelioid 24M, biphasic 15M, sarcomatoid 4.5M). Mesotheliomas with loss of BAP1 expression showed increased survival (20M vs 8M) and HD of p16 showed poor survival (9.5M vs 28M). However, if only epithelioid cases were analyzed, there was no trend toward increased survival with BAP1 loss (24M vs 22M) while HD of p16 still showed poor survival (17M vs 28M). Most of biphasic mesotheliomas and all sarcomatoid mesotheliomas harbor HD of p16. BAP1 loss and HD of BAP1 are observed in epithelioid and biphasic mesotheliomas, but not in sarcomatoid mesotheliomas. BAP1 immunostaining and FISH analysis of p16 help making distinction between epithelioid and biphasic mesothelioma as well as between benign and malignant mesothelial proliferation. p16 is a prognostic factor for patients with epithelioid mesothelioma, but BAP1 is not.