大肠癌和腺瘤组织中HPV16、18E6与p53、ras癌基因蛋白表达的研究

Study of expression of HPV16、18 E6,p53,p21ras oncoprotein in colorectal cancer

目的 探讨人乳头瘤病毒 16、18型感染与p5 3 ,p2 1ras癌基因协同 ,在大肠癌发生机制中的作用。 方法 采用SP免疫组化技术 ,检测 3 0例大肠腺瘤、10例腺瘤恶变、5 3例大肠腺癌和 3 0例正常大肠粘膜组织中HPV16、18E6,p5 3 ,p2 1ras蛋白并分析其相互关系。 结果 腺瘤、腺瘤恶变和腺癌组中E6,p5 3 ,p2 1ras的阳性表达分别为 3 6.7%、3 3 .3 %、40 .0 % ,60 .0 %、60 .0 %、70 .0 %和 5 4.7%、62 .2 %、71.7%。在腺瘤组中 ,随着上皮不典型性增生程度的加重 ,E6、p5 3、p2 1ras的阳性表达呈逐渐上升的趋势。腺瘤伴不典型性增生Ⅱ～Ⅲ级组中E6、p5 3、p2 1ras阳性表达显著高于腺瘤伴不典型性增生Ⅰ级 (P <0 .0 5 )。此外 ,腺瘤、腺瘤恶变及腺癌组中E6与p5 3 ,E6与 p2 1ras的双阳性表达均具显著相关性 (P <0 .0 5 )。在有淋巴结转移组中 ,E6的阳性表达和E6与 p5 3 ,E6与p2 1ras的双阳性表达均显著高于无淋巴结转移组 (P <0 .0 5 )。结论 本研究结果表明 :高危HPB16、18感染并在p5 3、ras癌基因的协同参与下 ,与本地区大肠癌的发生、发展过程密切相关 ,HPV 16、18感染后所致的 p5 3突变 /失活可能是大肠腺瘤恶变过程中的一个早期事件 ,在腺瘤中同时检测E6、p5 3、p2

? Objective To investigate the effect of HPV16、18 infection and cooperation of the active p53、p21ras oncogene on carcinogenesis of colorectal cancer.Methods HPV16、18 E6,p53,p21ras proteins were detected and analysed in 53 cases of colorectal adenocarcinomas,10 cases of adenoma with malignant transformation,30 cases of colorectal adenoma and 30 cases of normal colorectal mucosa tissue using S P immunohistochemical technique.Results The positive rates of E6,p53,p21ras were 36.7%,33.3%,40.0% in colorectal adenoma and 60.%(6/10),60.0%,70.0% in adenoma with malignant change,and 54.7%,62.2%,71.7% in colorectal adenocarcinoma,respectively.Coexpression of E6 and p53,E6 and p21ras in adenoma,adenoma with malignant change and adenocarcinoma group showed a significant correlation respectively(P<0.05),the positive expression of E6,p53,p21ras in adenoma of dysplasia Ⅱ～Ⅲ degree were higher than that in adenoma of dysplasia Ⅰ (P<0.05),positive coexpression of E6 and p53,E6 and p21ras were 26.7%(8/30),60.0%(6/10) in adenoma with malignant transfromation,respectively.Positive expression of E6 and coexpression of E6、p53,E6、p21ras were higher in lymph node metastasis group than in non lymph node metastais group(P<0.05).Conclusions HPV16、18 infection and mutation of p53,p21ras may be related to the tumorigensis and development of colorectal cancer,the mutation of p53 may be an early event.Detection of HPV16、18 E6,p53,p21ras oncoproteins in adenoma seems to be an attractive marker for the early diagnosis of colorectal cancer. 〔