Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Histopathology. 2021 Jun;78(7):1032-1042. doi: 10.1111/his.14324. Epub 2021 Apr 14.
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.
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.
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.
甲基硫腺苷磷酸化酶（MTAP）免疫组化表达是恶性间皮瘤中 CDKN2A 缺失的特异性标志物。然而，MTAP 表达与 MTAP 拷贝数之间的关系尚未被探索。
40 例恶性胸膜间皮瘤通过靶向下一代测序（29 例）、单核苷酸多态性微阵列（7 例）或两者（4 例）进行了特征描述。MTAP 和 CDKN2A 拷贝数与 MTAP 表达相关。27 例（68%）肿瘤存在 CDKN2A 缺失（14 例杂合性缺失；13 例纯合性缺失），其中 20 例（74%）存在 MTAP 共缺失（15 例杂合性缺失；5 例纯合性缺失）。没有肿瘤表现出 MTAP 缺失而没有 CDKN2A 共缺失。16 例（40%）肿瘤出现 MTAP 表达缺失，其对 MTAP 缺失的敏感性为 75%，特异性为 95%，对 CDKN2A 缺失的敏感性为 59%，特异性为 100%。40 例中有 9 例（23%）肿瘤显示 MTAP 染色不均匀，肿瘤细胞中 MTAP 缺失的百分比与 MTAP 缺失的分子检测相关。
MTAP 在胸膜间皮瘤中经常与 CDKN2A 共缺失。然而，这两个基因的纯合性缺失在少数肿瘤中发生（5/40；13%）；CDKN2A 缺失常与 MTAP 杂合性缺失或中性 MTAP 拷贝数同时发生；并且 MTAP 表达与 MTAP 杂合性缺失不一致相关。相应地，MTAP 免疫组化是 CDKN2A 缺失的一种高度特异性但仅中度敏感的检测方法。
