A Combination of MTAP and p16 Immunohistochemistry Can Substitute for CDKN2A Fluorescence In Situ Hybridization in Diagnosis and Prognosis of Pleural Mesotheliomas

Pleural mesothelioma (PM) is a rare cancer defined by 3 main histologic subtypes: epithelioid (EM), biphasic (BM), and sarcomatoid (SM). All have a very aggressive course. It is usually diagnosed [...]
Context.-Homozygous deletion (HD) of CDKN2A is one of the most frequent genetic abnormalities in pleural mesotheliomas. HD of CDKN2A by fluorescence in situ hybridization (FISH) is a reliable marker of malignancy in mesothelial proliferations; however, evaluation of CDKN2A deletion requires FISH. The 9p21 locus includes both CDKN2A and MTAP (methylthioadenosine phosphorylase); the latter is frequently codeleted with CDKN2A. Objective.-To examine the question of whether immunohistochemistry for MTAP and p16, the protein product of CDKN2A, can serve as a surrogate for CDKN2A HD by FISH. Design.-A random selection of 125 pleural mesothelioma cases was divided into 3 groups for evaluation of p16 and MTAP expression compared with FISH for CDKN2A deletion: 53 with HD, 39 with heterozygous deletion, and 33 without deletion. Results.-By itself, loss of p16 nuclear expression ( Conclusions.-MTAP immunohistochemical staining is a valid surrogate marker for CDKN2A HD by FISH; however, to obtain the same accuracy as the FISH assay, a combination of nuclear p16 and cytoplasmic MTAP staining is recommended. These findings correlate with prognosis. doi: 10.5858/arpa.2021-0331-OA