Scesnaite Asta, Jarmalaite Sonata, Mueller Maximillian, Agaimy Abbas, Zenk Johannes, Hartmann Arndt, Iro Heinrich, Peters Brigitte, Schwarz Stephan, Schneider-Stock Regine
Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
Head Neck. 2014 Sep;36(9):1258-67. doi: 10.1002/hed.23445. Epub 2013 Nov 27.
The purpose of this study was to determine the prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) inactivation in a group of 286 patients with salivary gland carcinoma and matched histologically normal tissues.
MGMT promoter methylation was studied in 36 patients with salivary gland carcinoma and 19 histologically matched normal tissues by pyrosequencing. MGMT protein expression was examined in 286 patients with salivary gland carcinomas and histologically matched normal tissues by immunohistochemistry on tissue microarrays. The results were correlated to demographic, clinicopathologic parameters, and disease follow-up data.
MGMT hypermethylation was significantly (p = .021) associated with the protein loss. MGMT loss was found in 39.2% of salivary gland carcinomas and was predominant in aggressive tumors (poorly differentiated, grade III, regional lymph node involved). MGMT loss significantly (p = .004) predicted poor clinical outcome of salivary gland carcinomas and defined high-risk subgroups in clinically favorable tumor groups.
We suggest that immunohistochemical evaluation of nuclear MGMT protein might serve as a tool for the prediction of overall survival in patients with salivary gland carcinoma.
本研究旨在确定O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）失活在286例涎腺癌患者及配对的组织学正常组织中的预后价值。
采用焦磷酸测序法对36例涎腺癌患者及19例组织学配对的正常组织进行MGMT启动子甲基化研究。采用免疫组织化学方法在组织芯片上检测286例涎腺癌患者及组织学配对的正常组织中的MGMT蛋白表达。将结果与人口统计学、临床病理参数及疾病随访数据进行关联分析。
MGMT高甲基化与蛋白缺失显著相关（p = 0.021）。在39.2%的涎腺癌中发现MGMT缺失，且在侵袭性肿瘤（低分化、III级、有区域淋巴结转移）中占主导。MGMT缺失显著（p = 0.004）预示涎腺癌患者临床预后不良，并在临床预后良好的肿瘤组中确定了高危亚组。
我们认为，对核MGMT蛋白进行免疫组织化学评估可作为预测涎腺癌患者总生存的一种工具。
