【作者】 陈积贤； 张洁； 任振华； 薛迪新； 吴伟力； 张仁虎； 余铭； 林道浙； 林肖； 梁美珍； 贺先伟； 徐平； 黄建武；

【Author】 Chen ji-xian Zhang jie Ren zheng-hua Xue di-xin Wu wei-li Zhang ren-hu Yu min Lin dao-zhe Lin xiao Huang jian-wu Liang mei-zhen He xian-wei Xu ping

【机构】 温州医学院附属第三医院肿瘤外科； 南通大学医学院； 安徽医科大学基础医学院； 温州医学院；

【摘要】 目的检测结直肠癌、腺瘤和各自的正常结直肠粘膜组织中p27基因启动子区CPG岛甲基化水平及其表达,并结合其临床病理参数进行分析,探讨与结直肠癌发生发展中的作用。方法应用甲基化特异性聚合酶链反应分析技术检测106例结直肠癌组织和各自的正常结直肠粘膜组织、22例腺瘤组织中p27基因启动子甲基化;用免疫组织化学S-P检测基因的蛋白表达。结果本组结直肠癌组织中p27甲基化阳性率为59.4%(63/106),腺瘤组织中为18.2%(4/22),而正常结直肠粘膜组织中为3.8%(4/106),前组与后两组间相比差异有统计学上的意义(P<0.05)。癌组织中p27甲基化阳性率:低分化组明显高于高中分化组(48%比24.7%,P<0.05);Dukes-A+B期组与C+D期组间差异有显著性(20.0%比41.2%,P<0.05);有无淋巴结转移两组间的阳性率差异有统计学意义(41.5%比23.1%,P<0.05);浸润深达浆膜层的结直肠癌组织中的甲基化阳性率与未达浆膜层组差异无统计学(32.5%比24.1%,P>005)结论结直肠癌组织中检测出有p27基因启动子甲基化,其基因蛋白表达率明显低于正常粘膜组织和腺瘤组织。p27基因的高甲基化与结直肠癌分化程度、浸润深度、Dukes分期及有无淋巴结转移有关。p27基因甲基化的发生,从正常粘膜组织到腺瘤、结直肠癌有逐渐增加趋势,可作为结直肠癌早期诊断、临床生物学行为及其预后判断均提供有利的参考依据。更多还原

【Abstract】 Objective:in order to investigate relationship between methylation of p27 gene and colorectal carcinogenesis,we detected the methylation level of CPG island in p27 gene promotor region in the colorectal carcinoma,colorectal adenoma,normal mucous membrane tissue and analyze their relationship according to clinicopathologic feature in colorectal carcinoma.Methods methylation of p27 gene promotor region and p27 protein expression were detected respectively by methylation specificity polymerase chain reaction and immunohistochemical staining SP in 106 cases colorectal carcinoma and their own adjacent normal mucous membrane tissue and 22 cases colorectal adenoma tissue.Results The positive expression rate of p27 gene methylation was significant statistically different in colorectal carcinoma tissue compared with normal mucous membrane and colorectal adenoma tissue(P<0.05).Their positive expression rate were 59.4%(63/106) ,18.2%(4/22) and 3.8%(4/106) respectively in colorectal carcinoma tissue,colorectal adenoma and normal mucous membrane tissue.Among colorectal carcinoma tissues,It was obviously different to the positive expression rate of p27 gene methylation between groups as follows except the last one:the poorly differentiated group vs well-differentiated group(48%vs24.7%,P<0.05),Dukes-A+B stage group vs Dukes C+D stage group(20.0%vs41.2%,P<0.05),lymph nodes metastases group vs without lymph nodes metastases group (41.5%vs23.1%,P<0.05),infiltrating to serosa group vs without infiltrating to serosa group(32.5%vs24.1%, P>005).Conclusion the methylated p27 gene protein expression in colorectal carcinoma was obviously lower than normal mucous membrane and colorectal adenoma tissue.the hypsi- methylation of p27 gene in colorectal carcinoma was significantly associated with differentiation、invasive depth、Dukes stage、lymph node metastasis.For the level of methylation of p27 gene,an increased tendency was found from normal mucous membrane tissue,colorectal adenoma to colorectal carcinoma,So it may be used as an imporiant parameter in early diagnosis and evaluating the clinic biological behavior and prognosis of colorectal carcinoma.更多还原