Assessing the Role of BAP1 Loss and p16 Deletion in the Diagnosis of Mesothelioma

According to a recent study, BRCA1-associated protein (BAP1) immunohistochemistry (IHC) and p16 (CDKN2A) deletion contribute to providing a definitive diagnosis of mesothelioma. The results appeared in the European Review for Medical and Pharmacological Sciences.

“The cytological diagnosis of mesothelioma is a controversial issue, and definitive diagnosis often requires ancillary tests. The aim of this study was to investigate the contribution of [BAP1] loss and p16 [CDKN2A] homozygous deletion (HD) on the early diagnosis of mesothelioma in effusion fluids,” the researchers wrote.

In this study, researchers assessed 21 pleural and peritoneal fluid samples diagnosed with atypical mesothelial proliferation between 2019 and 2022. They also re-examined slides of the cases that underwent BAP1 IHC. HD of p16 (CDKN2A) was investigated using the fluorescence in situ hybridization (FISH) method in cell blocks of cytology samples, and more than 100 atypical mesothelial cells were counted in each case, with the HD threshold value specified as >10%.

According to the results, BAP1 loss was observed in 69% of 16 cases. Also, HD deletion of p16 (CDKN2A) was observed in 58% patients with FISH. The investigators noted that the HD threshold value was 10% to 20% in 6 of the cases, 30% to 50% in 3 cases, and above 90% in 2 cases. Positivity was seen with at least 1 method in 86% of pleural mesothelioma cases that underwent both BAP1 IHC and p16 (CDKN2A) with FISH.

“Asbestos exposure in areas where mesothelioma is endemic and/or the presence of proliferating mesothelial cells in cytological examination are important clues for diagnosis. In controversial cases, BAP1 IHC should be the first step in an ancillary test. Although the FISH method applied to cell blocks has cytology-specific limitations and difficulties, investigating the p16 (CDKN2A) deletion with FISH in selected cases will contribute to the diagnosis,” the researchers concluded.