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目的分析胃癌组织中肿瘤抑制基因启动子区甲基化状态及其与临床分期、分型的关系。方法采用甲基化特异性聚合酶链反应方法,检测106例胃癌及其邻近胃小凹上皮、16例慢性胃炎小凹上皮石蜡标本中 E 钙黏素(E-CD)、错配修复酶 hMLHl、APC 和6-氧-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)基因启动子区甲基化状态,并对其中46例胃癌采用免疫组化方法检测 E-CD 蛋白表达情况。结果在胃癌、胃癌邻近小凹上皮及慢性胃炎小凹上皮中,基因甲基化频率分别为72.6%(77/106)、44.3%(47/106)和12.5%(2/16),三者间差异有统计学意义(P<0.01)。Laurén 弥漫型胃癌甲基化(80.6%,50/62)明显高于肠型胃癌甲基化(61.4%,27/44),两者间差异有统计学意义(P<0.01)。甲基化与患者的年龄、性别、Ming 分型及区域淋巴结转移无关(均 P>0.05),甲基化与胃癌的浸润深度、pTNM 分期和分化程度有关(均 P<0.05)。行 E-CD 蛋白检测的46例胃痛中,22例有 E-CD 基因甲基化,其中20例(90.9%)E-CD 蛋白呈异质性减弱或基本消失表达;24例无 E-CD基因甲基化,其中9例(37.5%)E-CD 蛋白呈异质性减弱或基本消失表达,两者间差异有统计学意义(P<0.01)。结论上述肿瘤抑制基因启动了区甲基化可能是胃癌发生的早期事件。胃癌 E-CD 基因甲基化与 E-CD 蛋白异质性减弱或消失表达密切相关。
Objective To analyze the methylation status of tumor suppressor gene promoter region in gastric carcinoma and its relationship with clinical stage and classification. Methods E-cadherin (E-CD), mismatch repair enzyme hMLH1 , APC and 6-O-methylguanine-DNA methyltransferase (MGMT) gene promoter region methylation status, and 46 cases of gastric cancer by immunohistochemistry to detect E-CD protein expression. Results The frequency of methylation was 72.6% (77/106), 44.3% (47/106) and 12.5% (2/16) in gastric cancer, adjacent small concave gastric epithelium and chronic gastritis small concave epithelium, respectively The difference was statistically significant (P <0.01). Laurén diffuse gastric cancer methylation (80.6%, 50/62) was significantly higher than intestinal type gastric cancer methylation (61.4%, 27/44), the difference was statistically significant (P <0.01). Methylation was not associated with age, gender, Ming classification and regional lymph node metastasis (all P> 0.05). Methylation was related to the depth of invasion, pTNM stage and differentiation (all P <0.05). Twenty-four of the 46 cases of gastric pain detected by E-CD protein had methylation of E-CD gene. Among them, E-CD protein of 20 cases (90.9%) showed weakened or almost disappeared expression; 24 cases had no E-CD Gene methylation, including 9 cases (37.5%) of E-CD protein heterogeneity decreased or disappeared, the difference between the two was statistically significant (P <0.01). Conclusion The above-mentioned tumor suppressor gene promoter methylation may be an early event in gastric carcinogenesis. The methylation of E-CD gene in gastric cancer is closely related to the weakened or disappeared expression of E-CD protein.