Huang Sung-Hsien, Lee Herng-Sheng, Mar Kwei, Ji Dar-Der, Huang Mao-Suan, Hsia Kan-Tai
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Jun;109(6):883-9. doi: 10.1016/j.tripleo.2009.12.019.
O(6)-methylguanine-DNA methyltransferase (MGMT) ameliorates mutagenic, carcinogenic, and cytotoxic adducts from O(6)-methylguanine in DNA through a direct reversal mechanism. Decreased expression of MGMT has been reported in a variety of human malignant tumors. The purpose of this study was to clarify the correlation of MGMT expression levels in oral squamous cell carcinoma (OSCC) with promoter hypermethylation and with betel quid chewing and cigarette smoking.
MGMT protein expression in 63 cases of oral squamous cell carcinoma by immunohistochemistry was investigated. Methylation status of the MGMT was analyzed by methylation-specific PCR. Correlation with clinicopathologic parameters was then tested by statistical analysis.
MGMT immunohistochemistry revealed nuclear staining in normal epithelium, whereas 47 (75%) of 63 OSCC tumors were devoid of MGMT expression and this was related to tumor cell differentiation. Furthermore, the association between loss of MGMT expression and promoter hypermethylation was significant. Lacking protein expression for MGMT in OSCC was also associated with the use of betel quid.
The results suggest that the absence of MGMT expression, which would seem to be associated with promoter hypermethylation, is related to betel quid chewing and, thus, in turn, might be a significant event in oral carcinogenesis.
O(6)-甲基鸟嘌呤-DNA甲基转移酶（MGMT）通过直接逆转机制改善DNA中O(6)-甲基鸟嘌呤的诱变、致癌和细胞毒性加合物。已有报道称在多种人类恶性肿瘤中MGMT表达降低。本研究的目的是阐明口腔鳞状细胞癌（OSCC）中MGMT表达水平与启动子高甲基化以及与嚼槟榔和吸烟的相关性。
通过免疫组织化学研究63例口腔鳞状细胞癌中MGMT蛋白的表达。采用甲基化特异性PCR分析MGMT的甲基化状态。然后通过统计分析检测其与临床病理参数的相关性。
MGMT免疫组织化学显示正常上皮细胞核染色，而63例OSCC肿瘤中有47例（75%）无MGMT表达，这与肿瘤细胞分化有关。此外，MGMT表达缺失与启动子高甲基化之间的关联显著。OSCC中缺乏MGMT蛋白表达也与嚼槟榔有关。
结果表明，MGMT表达缺失似乎与启动子高甲基化有关，与嚼槟榔有关，因此，反过来，可能是口腔致癌过程中的一个重要事件。
