人乳头状瘤病毒在食管癌中的表达及其作用

Expression and Effect of Human Papillomavirus in Esophageal Carcinoma

背景:人乳头状瘤病毒(HPV)感染与宫颈癌和口腔鳞状细胞癌的发生密切相关,但其与食管癌的关系及其所致相关基因表达的变化尚不十分清楚。目的:研究HPV在食管癌中的表达,探讨其对相关基因蛋白表达的影响。方法:以DNA原位杂交法检测HPV16基因的表达,以免疫组化方法检测HPV16E6、突变型p53、p21WAF1、pRb和p16INK4a蛋白的表达。结果:食管癌组织中HPV16DNA的阳性率显著高于正常对照组(65.6%对10.0%,P<0.001),HPV16E6蛋白的表达率亦显著高于正常对照组(58.9%对15.0%,P<0.001);突变型p53蛋白的表达率显著高于正常对照组(53.3%对45.0%,P<0.05),p21WAF1、pRb和p16INK4a蛋白的表达率则显著低于正常对照组(22.2%对65.0%、23.3%对55.0%和35.6%对85.0%,P<0.001)。食管癌组织中HPV16E6蛋白与突变型p53蛋白的表达呈正相关,与p21WAF1、pRb和p16INK4a蛋白的表达呈负相关(P<0.01)。结论:HPV感染是食管癌发生的重要危险因素之一,其可能通过p53突变和p21WAF1、pRb、p16INK4a失活参与了食管癌的发生。

Background： Human papillomavirus （HPV） infection is reported to be closely associated with the pathogenesis of cervical carcinoma and oral squamous cell carcinoma. However, the relationship of HPV and esophageal carcinoma and the changes of related genes expression induced by HPV remain uncertain. Aims： To investigate the expression of HPV and its effect on the protein expression of related genes in esophageal carcinoma. Methods： DNA in situ hybridization was used to detect the expression of HPV 16 gene, and the expression of HPV 16 E6, mutative p53, p21WAF1, pRb and p l6INK4a proteins were detected by immunohistochemistry. Results： In esophageal carcinoma tissues, the positivity rate of HPV16 DNA was significantly higher than that in the controls （65.6% vs. 10.0%, P〈0.001）, so did the expression of HPV 16 E6 protein （58.9% vs. 15.0%, P〈O.001）. The positivity rate of mutative p53 protein was significantly higher in esophageal carcinoma tissues than that in the controls （53.3% vs. 45.0%, P〈0.05）, while the expression rates ofp21WAF1, pRb and pl6INK4a proteins were significantly lower than those in the controls （22.2% vs. 65.0%, 23.3% vs. 55.0% and 35.6% vs. 85.0%, respectively, P〈0.001）. The expression of HPV16 E6 protein was positively correlated with the expression of mutative p53 protein and negatively correlated with the expression of p21WAF1, pRb and p16INK4a proteins in esophageal carcinoma tissues （P〈0.01）. Conclusions： HPV infection is one of the risk factors of esophageal carcinoma. HPV is suggested to play an important role in the pathogenesis of esophageal carcinoma by the pathway of p53 mtitation and p21WAF1, pRb and p16INK4a inactivation.