Correlation of methylthioadenosine phosphorylase (MTAP) protein expression with MTAP and CDKN2A copy number in malignant pleural mesothelioma. Issue 7 (14th April 2021)

• Record Type: Journal Article
• Authors: Chapel, David B; Dubuc, Adrian M; Hornick, Jason L; Sholl, Lynette M
• Is Part Of: Histopathology. Volume 78:Issue 7(2021)
• Page Start: 1032
• Page End: 1042
• Publication Date: 2021-04-14
• Subjects: cytogenetics -- high‐throughput nucleotide sequencing -- immunohistochemistry -- mesothelioma; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.14324
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : Aims: Methylthioadenosine phosphorylase (MTAP) immunohistochemical expression is a specific marker of CDKN2A deletion in malignant mesothelioma. However, the relationship of MTAP expression with MTAP copy number remains unexplored. Methods and results: Forty malignant pleural mesotheliomas were characterised by targeted next‐generation sequencing (29), single‐nucleotide polymorphism microarray (seven), or both (four). MTAP and CDKN2A copy numbers were correlated with MTAP expression. Twenty‐seven (68%) tumours showed CDKN2A deletion (14 heterozygous; 13 homozygous), of which 20 (74%) showed MTAP codeletion (15 heterozygous; five homozygous). No tumours showed MTAP deletion without CDKN2A codeletion. Loss of MTAP expression was seen in 16 (40%) tumours, and was 75% sensitive and 95% specific for MTAP deletion, and 59% sensitive and 100% specific for CDKN2A deletion. Nine of 40 (23%) tumours showed heterogeneous MTAP staining, and the percentage of tumour cells with MTAP loss correlated with molecular detection of MTAP deletion. Conclusions: MTAP is frequently codeleted with CDKN2A in pleural mesothelioma. However, homozygous deletion of both genes occurs in a minority of tumours (5/40; 13%); CDKN2A deletion often co‐occurs with heterozygous MTAP deletion or neutral MTAP copy number; and MTAP expression correlates inconsistently with heterozygous MTAP deletion. Correspondingly, MTAP immunohistochemistry is a highly specific but only moderately sensitive assay for CDKN2A deletion. Abstract :