散发性结直肠癌、腺瘤组织中hMLH1和突变型p53表达

目的]探讨hMLH1和p53基因在散发性结直肠癌发生机制中所起的作用。方法]采用PV-6000二步法免疫组化检测技术对60例散发性结直肠癌，45例大肠腺瘤和26例正常大肠黏膜石蜡切片进行hMLH1和p53表达的检测。结果]（1）60例散发性结直肠癌hMLH1蛋白阴性表达和p53蛋白阳性表达分别为11例（18．3％）和32例（53.3％），hMLH1蛋白阴性表达和p53蛋白阳性表达与患者年龄、肿瘤部位、组织学类型和分化程度密切相关（P〈0．05或P〈0．01），而与患者性别、肿瘤大体类型、肿块大小、浸润深度、淋巴结及远处转移与否和患者的Duke’s分期均无显著相关性（P〉0．05）。（2）大肠腺瘤患者p53蛋白阳性表达与患者腺瘤部位、组织学类型和不典型增生程度密切相关（P〈0．05），而与患者性别、年龄无显著相关性（P〉0．05）。（3）散发性结直肠癌中hMLH1蛋白阴性表达组p53蛋白阳性表达率（18.2％，2/11）低于阳性表达组（61．2％，30／49）（P〈O．05）。结论]（1）大部分散发性结直肠癌是沿染色体不稳定途径发生，其中抑癌基因p53的突变起重要作用。同时，一定比例的散发性结直肠癌中存在错配修复基因的缺陷，并具有相对特殊的临床病理特征。（2）大肠腺瘤组织中有一定比例的hMLH1蛋白阴性表达和p53蛋白阳性表达，提示hMLH1和p53基因的突变可能是散发性结直肠癌发生的早期事件之一。

Expression of hMLH1 and p53 in Sporadic Colorectal Carcinoma and Colorectal Adenoma

Purpose] To explore the role of hMLH1 and p53 gene in the carcinogenesis of sporadic colorectal carcinoma.Methods] The expression of hMLH1 and p53 protein in 60 cases with sporadic colorectal carcinoma,45 cases with colorectal adenoma and 26 cases with normal intestinal mucosa were detected by PV-6000 immunohistochemical method.Results](1)Negative expression of hMLH1 protein and positive expression of p53 protein were detected in 11 cases(18.3%)and 32 cases(53.3%)with sporadic colorectal carcinoma respectively.Negative expression of hMLH1 protein and positive expression of p53 protein were closely related to patient's age,tumor location,histological type and histological grade(P<0.05 or P<0.01),but were not correlated with patient's gender,tumor gross type,tumor size,invasive depth,lymph node metastasis,distant metastasis and Duke's stage(P>0.05).(2)The positive expression of p53 protein was closely related to adenoma site,histological type and dysplasia grade,but it was not correlated with patient's gender and age(P>0.05).(3)The positive expression of p53 protein in the group of hMLH1 protein negative expression(18.2%,2/11)was lower than that in the group of hMLH1 protein positive expression(61.2%,30/49)in sporadic colorectal carcinoma(P<0.05).Conclusions](1)Majority of sporadic colorectal carcinoma occurs via the chromosomal instability pathway in which the p53 gene plays an important role,meanwhile there is a subset of sporadic colorectal carcinoma displaying mismatch repair(MMR)defect with specially clinical and pathological features.(2)There is a subset of colorectal adenoma displaying negative expression of hMLH1 protein and positive expression of p53 protein.Mutation of hMLH1 gene and p53 gene may be an early event of carcinogenesis in sporadic colorectal carcinoma.