食管鳞状细胞癌中MT3基因CpG岛甲基化及其临床意义

Clinical significance of CpG island methylation of MT3 gene in squamous cell carcinoma of esophagus

目的 探讨食管癌中 MT3基因 Cp G岛甲基化的情况及其临床意义。方法 选取切除的食管鳞癌标本4 7例 ,提取肿瘤、上切缘、下切缘及转移淋巴结的标本蜡块 DNA,经重亚硫酸化处理后 ,进行 COBRA分析 ,所得结果与各临床病理参数及随访资料进行比较。结果 全组有 10例 (2 1.3% )肿瘤组织发现 MT3基因甲基化 ,其中 1例呈原位癌样改变的上切缘也检测到甲基化。全组 35枚转移淋巴结中共发现 15枚 (4 2 .9% )甲基化 ,与肿瘤组织相比 ,差异有显著性 (P=0 .0 37,χ2 =4 .35 5 )。原发肿瘤存在甲基化 10例患者中 ,每例有 (5 .7± 3.6 0 )枚转移淋巴结。而不存在甲基化的 37例转移淋巴结数为 (3.2± 2 .13)枚 ,两者比较差异有显著性 (P=0 .0 18)。肿瘤组织的甲基化情况与患者的性别、年龄、烟酒嗜好、肿瘤分期及分化程度均无关 (P值均 >0 .0 5 ,χ2 检验 )。结论 MT3基因Cp G岛甲基化与食管鳞癌的淋巴结转移状况关系密切 ,作为一个独立的预后因素 。

Objective To detect CpG island methylation of MT3 gene in squamous cell carcinoma of the esophagus and to explore its clinical significance. Methods Forty-seven patients were investigated with esophageal cancer operated between May 2000 and August 2001. Total DNA samples were extracted from the blocks of tumors, upper margins, lower margins and metastatic lymph nodes of these patients. After treated with bisulfite, the DNA was amplified and digested by combined bisulfite restrict analysis (COBRA). The correlation between methylation of MT3 and clinicopathological factors of esophageal cancer was analysed. Results Hypermethylation of MT3 was found in 10 cases (21.3%) of the 47 blocks of tumor tissue. In one of these 10 patients, hypermethylation was also found in one block of upper margin which was demonstrated as carcinoma in situ. Hypermethylation was also found in 15 (42.9%) of the 35 blocks of lymph nodes, which was higher in rate of hypermethylation than that of tumor tissues (P=0.037, χ~2=4.355). In patients who showed hypermethylation in primary tumor, the number of metastatic lymph nodes was 5.7±3.60, compared with 3.2±2.13 in these who did not show hypermethylation in primary tumor (P=0.018). The hypermethylation of tumor tissues had no correlation with gender, age, smoking and alcohol drinking of patients, histological differentiation and stage of disease (P>0.05). Conclusions CpG island methylation of MT3 is associated with metastasis of lymph nodes in esophageal cancer, and as an independent prognostic factor. It may play a positive role in the occurrence and development of carcinoma of the esophagus.