hMLH1和RASSF1A在食管癌组织中的表达及其与患者预后的关系

Correlation between hMLH1 and RASSF1A expression and prognosis of esophageal carcinoma

目的:探讨食管鳞癌组织中hMLH1和RASSF1A基因表达及其对预后的影响.方法:采用原位杂交技术检测hMLH1基因、免疫组织化学法检测RASSF1A基因在60例食管鳞癌患者中的表达,应用Cox回归模型和Kaplan-Meier生存曲线分析其与患者预后的关系.结果:在食管鳞癌组织中hMLH1 mRNA表达显著低于正常黏膜组织(41.67%vs90.00%,P<0.01),RASSF1A蛋白表达低于食管正常黏膜组织(80%vs100%,P<0.05).hMLH1和RASSF1A的表达与TNM分期、食管癌浸润深度、淋巴结转移和肿瘤大小相关(均P<0.05),但与民族无关;RASSF1A与hMLH1表达呈正相关(r=0.338,P<0.01);本组病例5年总生存率为35%(21/60),单因素生存分析表明,食管癌hMLH1高表达组5年生存率高于低表达组,差异有统计学意义(P<0.05);RASSF1A高表达组较低表达组有生存优势,但差异无统计学意义;Cox模型多因素分析表明,hMLH1和RASSF1A不是影响生存期的独立因素,而肿瘤浸润深度和TNM分期均是影响生存期的独立因素(P<0.05).结论:hMLH1和RASSF1A在食管癌组织中表达均较低,其表达水平与食管肿瘤的发生发展有一定的关系,结合临床病理可作为判断预后的指标.

AIM：To investigate the expression of human mutL homologue 1（hMLH1）and Ras association domain family 1A（RASSF1A）in esophageal squamous cell carcinoma（ESCC）and to analyze their prognostic value.METHODS：The expression of hMLH1 mRNA and RASSF1A protein in 60 specimens of esophageal cancer was detected by in situ hybridization（ISH）and immunohistochemistry,respectively.The relationship of hMLH1 and RASSF1A expression with ESCC prognosis was evaluated using Cox regression model and Kaplan-Meier survival curve analysis.RESULTS：The positive rates of hMLH1 and RASSF1A expression in esophageal carcinoma were significantly lower than those in normal esophageal tissue（41.67%vs 90.00%,80.00% vs 100.00%;both P0.05）.The expression of hMLH1 and RASSF1A was correlated with tumor TNM stage,invasion depth,lymph node metastasis,and tumor size（all P0.05）,but not with patient＇s nationality（P0.05）.The expression of RASSF1A was positively correlated with that of hMLH1（r=0.338,P0.01）.The five-year overall survival rate for all the patients was 35% （21/60）.Univariate survival analysis suggested that the five-year survival rate for patients with positive expression of RASSF1A was higher than that for patients with negative expression of RASSF1A though the difference was not significant（P0.05）.Patients with positive expression of hMLH1 had a significantly higher survival rate compared to those with negative expression of hMLH1（P0.05）.Cox multivariate analysis indicated that tumor invasion depth and TNM stage were independent prognostic factors affecting survival of ESCC patients（both P0.05）.CONCLUSION：Both hMLH1 and RASSF1A were weakly expressed in ESCC.The expression of hMLH1 and RASSF1A was positively correlated with ESCC progression.Expression of hMLH1 and RASSF1A might be used as a prognostic parameter in ESCC patients.