Loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression is a common event in cancer leading to a critical vulnerability of cancer cells towards anti-cancer drugs. Homozygous MTAP deletions result in a complete expression loss that can be detected by immunohistochemistry (IHC). In this study, a tissue microarray containing 17,078 samples from 149 different tumor entities was analyzed by IHC, and complete MTAP loss was validated by fluorescence in situ hybridization. MTAP loss was observed in 83 of 149 tumor categories, including neuroendocrine neoplasms (up to 80%), Hodgkin lymphoma (50.0%), mesothelioma (32.0% to 36.8%), gastro-intestinal adenocarcinoma (4.0% to 40.5%), urothelial neoplasms (10.5% to 36.7%), squamous cell carcinomas (up to 38%), and various types of sarcomas (up to 20%) and non-Hodgkin lymphomas (up to 14%). Homozygous MTAP deletion was found in 90% to 100% of cases with MTAP expression loss in most tumor categories. However, neuroendocrine tumors, Hodgkin lymphomas, and other lymphomas lacked MTAP deletions. MTAP deficiency was significantly linked to unfavorable tumor phenotype in selected tumor entities and the presence of PD-L1 expression on tumor cells, absence of PD-L1 expression on immune cells, and a low density of CD8+ lymphocytes. In summary, MTAP deficiency can occur in various tumor entities and is linked to unfavorable tumor phenotype and noninflamed tumor microenvironment, but is not always related to deletions. MTAP IHC is of considerable diagnostic value for the detection of neoplastic transformation in multiple different applications.

中文翻译：

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人类癌症中 S-甲基-5'-硫代腺苷磷酸化酶 (MTAP) 缺陷的患病率：对来自 149 种不同肿瘤类型的 13,067 个肿瘤进行的组织微阵列研究。


S-甲基-5'-硫代腺苷磷酸化酶 (MTAP) 表达的丧失是癌症中的常见事件，导致癌细胞对抗癌药物的严重脆弱性。纯合 MTAP 缺失会导致表达完全丧失，可通过免疫组织化学 (IHC) 检测到。在这项研究中，通过 IHC 分析了包含来自 149 个不同肿瘤实体的 17,078 个样本的组织微阵列，并通过荧光原位杂交验证了 MTAP 的完全丢失。在 149 个肿瘤类别中的 83 个肿瘤类别中观察到 MTAP 丢失，包括神经内分泌肿瘤（高达 80%）、霍奇金淋巴瘤（50.0%）、间皮瘤（32.0% 至 36.8%）、胃肠腺癌（4.0% 至 40.5%）、尿路上皮癌肿瘤（10.5%至36.7%）、鳞状细胞癌（高达38%）、各种类型的肉瘤（高达20%）和非霍奇金淋巴瘤（高达14%）。大多数肿瘤类别中 90% 至 100% 的 MTAP 表达缺失病例均发现纯合 MTAP 缺失。然而，神经内分泌肿瘤、霍奇金淋巴瘤和其他淋巴瘤缺乏 MTAP 缺失。 MTAP 缺陷与选定肿瘤实体中不利的肿瘤表型、肿瘤细胞上存在 PD-L1 表达、免疫细胞上不存在 PD-L1 表达以及 CD8+ 淋巴细胞密度低显着相关。总之，MTAP 缺陷可发生在各种肿瘤实体中，并与不利的肿瘤表型和非炎症肿瘤微环境有关，但并不总是与缺失相关。 MTAP IHC 对于多种不同应用中肿瘤转化的检测具有相当大的诊断价值。