Kohya Naohiko, Miyazaki Kohji, Matsukura Shiroh, Yakushiji Hiroyuki, Kitajima Yoshihiko, Kitahara Kenji, Fukuhara Masao, Nakabeppu Yusaku, Sekiguchi Mutsuo
Department of Surgery, Saga Medical School, Saga, Japan.
Ann Surg Oncol. 2002 May;9(4):371-9. doi: 10.1007/BF02573872.
O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that transfers methyl groups from O(6)-methylguanine to itself. Alkylation of DNA at the O(6) position of guanine is an important step in the induction of mutations in the organism by alkylating agents. The O(6)-methyl G:T mismatch is recognized by the mismatch-repair (MMR) pathway. The biliary duct is highly exposed to alkylating agents because of its anatomical location.
We examined 39 surgically resected gallbladder carcinomas and 35 extrahepatic bile duct carcinomas and evaluated the expression of MGMT and MMR protein (hMLH1 and hMSH2) by immunohistochemical staining.
MGMT-negative staining was detected in 59.0% of gallbladder carcinoma specimens and 60.0% of extrahepatic bile duct carcinoma specimens. In gallbladder carcinoma, hMLH1- and hMSH2-negative staining was observed in 51.3% and 59.0%, respectively, whereas in extrahepatic bile duct carcinoma, the respective values were 57.1% and 65.7%. MGMT-negative staining correlated with hepatic invasion in gallbladder carcinoma and with poor prognosis in both types of tumor. Furthermore, a combined MGMT and MMR status was shown to be a more significant prognostic biomarker in both tumor types.
Combined MGMT and MMR is a possible prognostic marker that probably reflects an accumulation of genetic mutations.
O(6)-甲基鸟嘌呤-DNA甲基转移酶（MGMT）是一种DNA修复酶，可将甲基从O(6)-甲基鸟嘌呤转移至自身。鸟嘌呤O(6)位的DNA烷基化是烷基化剂诱导机体发生突变的重要步骤。O(6)-甲基G:T错配可被错配修复（MMR）途径识别。由于胆管的解剖位置，其高度暴露于烷基化剂。
我们检查了39例手术切除的胆囊癌和35例肝外胆管癌，并通过免疫组织化学染色评估了MGMT和MMR蛋白（hMLH1和hMSH2）的表达。
59.0%的胆囊癌标本和60.0%的肝外胆管癌标本检测到MGMT阴性染色。在胆囊癌中，hMLH1和hMSH2阴性染色分别见于51.3%和59.0%，而在肝外胆管癌中，相应比例分别为57.1%和65.7%。MGMT阴性染色与胆囊癌的肝侵犯以及两种肿瘤的预后不良相关。此外，MGMT和MMR联合状态在两种肿瘤类型中均显示为更显著的预后生物标志物。
MGMT和MMR联合检测可能是一种预后标志物，可能反映了基因突变的积累。
