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目的 探讨人乳头瘤病毒 16、 18型感染与 p5 3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 30例大肠腺瘤、 10例腺瘤恶变、 5 3例大肠腺癌和 30例正常大肠粘膜组织中 HPV16、 18E6 ,p5 3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的阳性表达分别为 36 .7% (11/ 30 )、 33.3% (10 / 30 ) ,6 0 .0 % (6 /10 )、 6 0 .0 % (6 / 10 )和 5 4.7% (2 9/ 5 3)、 6 2 .2 % (33/ 5 3) ,而正常组均呈阴性表达。在腺瘤组中 ,随着上皮不典型性增生程度的加重 ,E6、 p5 3的阳性表达呈逐渐上升的趋势。腺瘤、腺瘤恶变及腺癌组中 E6与 p5 3的双阳性表达具显著相关性 (P <0 .0 5 )。在有淋巴结转移组中 ,E6的阳性表达和 E6与 p5 3的双阳性表达均显著高于无淋巴结转移组 (P <0 .0 5 )。结论 高危 HPV16、 18感染并在 p5 3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蛋白有可能成为大肠癌早期诊断的免疫学指标之一。
Objective To investigate the role of human papillomavirus type 16 and 18 in cooperation with p5 3 oncogene in the pathogenesis of colorectal cancer. Methods SP immunohistochemistry was used to detect the expression of HPV16, 18E6 and p5 3 in 30 cases of colorectal adenoma, 10 cases of adenoma, 53 cases of colorectal adenocarcinoma and 30 cases of normal colorectal mucosa. Results The positive expression rates of E6 and p5 3 in adenoma, adenoma and adenocarcinoma were 36.7% (11/30), 33.3% (10/30) and 60.0% (6/10), respectively 6 0. 0% (6/10) and 5 4.7% (2 9/5 3), 62.2% (33/5 3) respectively, while the normal group showed negative expression. In the adenoma group, the positive expression of E6, p5 3 showed a gradual upward trend as the degree of epithelial dysplasia increased. Adenocarcinoma, adenoma malignant and adenocarcinoma group E6 and p5 3 double positive expression was significantly correlated (P <0. 05). In cases with lymph node metastasis, the positive expression of E6 and double positive expression of E6 and p5 3 were significantly higher than those without lymph node metastasis (P <0.05). Conclusions High-risk HPV16 and HPV18 infection is closely related to the occurrence and development of colorectal cancer in the region with the cooperation of p5 3 oncogene. The mutation / inactivation of p53 caused by HPV 16 and 18 infection may be caused by colorectal adenoma An early event in malignant transformation, simultaneous detection of E6 and p53 proteins in adenomas may be one of the immunological indicators of early diagnosis of colorectal cancer.