HPV16/18-E6、p53和MDM2蛋白在人喉鳞癌中的表达及相关性研究

Expressions of HPV16/18-E6, p53 and MDM2 proteins in human laryngeal squamous cell carcinoma and their relationship with development and progression of laryngeal squamous cell carcinoma

目的：探讨HPV16／18-E6、p53和MDM2蛋白在人喉鳞状细胞癌（鳞癌）组织中的表达及其在喉鳞癌发生和发展过程中的相互关系。方法：用EnVision免疫组织化学法检测72例喉鳞癌、24例喉癌前病变、15例声带息肉和8例癌周正常喉组织标本中HPV16／18-E6、p53和MDM2蛋白的表达并比较，对喉鳞癌与临床病理因素进行相关性分析。、结果：癌周正常喉组织、声带息肉、喉癌前病变和喉鳞癌组织中HPV16／18-E6蛋白的阳性表达率分别为0（0／8）、6．7％（1／15）、12．5％（3／24）和37．5％（27／72），p53蛋白的阳性表达率分别为0（0／8）、13．3％（2／15）、25．0％（6／24）和52．8％（38／72），MDM2蛋白的阳性表达率分别为0（0／8）、6．7％（1／15）、37．5％（9／24）和70．8％（51／72），HPV16／18-E6、p53和MDM2蛋白的阳性表达在声带息肉、喉癌前病变与喉鳞癌组之间均有显著性差异（P〈0．05）。HPV16／18-E6蛋白和MDM2蛋白的阳性表达在病理Ⅰ～Ⅲ级肿瘤之间呈明显升高趋势，有显著性差异（P〈0．05）。HPV16／18E6蛋白的阳性表达与临床分期和淋巴结转移明显相关（P〈0．05）。p53蛋白阳性表达与HPV16／18-E6蛋白、MDM2蛋白阳性表达有显著正相关性（P〈0．05）。结论：HPV16／18-E6、MDM2蛋白的过表达和p53的失活与人喉鳞癌的发生发展密切相关。

Objective：To study the expressions of human papillomavirus type 16/18-E6 （HPV16/18-E6）, p53, and murine double minute-2 （MDM2） proteins in patients with laryngeal squamous cell carcinoma （LSCC） and their relationship with the development/progression of LSCC. Methods： The expressions of HPV16/18-E6, p53, and MDM2 proteins were detected by immunohistochemical method in 72 LSCC specimens, 24 specimens of precancerous larynx, 15 specimens of vocal cord polyp, and 8 normal laryngeal specimens, and their relations with clinicopathological factors of LSCC were statistically analyzed. Results： The positive rates of HPV16/18-E6 protein in the normal laryngeal, vocal cord polyp, precancerous larynx, and LSCC specimens were 0（0/8）, 6.7%（1/15）, 12.5%（3/24）, and 37.5%（27/72）; of p53 protein were 0（0/8）, 13.3%（2/15）, 25.0%（6/24）, and 52.8% （38/72） ; and of MDM2 protein were 0（0/8）, 6.7% （1/15）, 37.5 % （9/24）, and 70.8M （51/72）, respectively. The expressions of HPV16/18-E6, p53, and MDM2 were significantly different between the vocal cord polyp, the precacerous larynx, and the LSCC （P〈0.05）. The positive rates of HPV16/18-E6 and MDM2 protein in LSCC specimens increased significantly with the increase of histopathological grades （Ⅰ-Ⅲ） （P〈 0.05）. The positive rates of HPV16/18-E6 protein were positively correlated with the clinical staging and lymph nodes metastasis of LSCC （P〈0. 05）. The expression of p53 was positively correlated with the expression of HPV16/18-E6 and MDM2 in LSCC patients （P〈0.05）. Conclusion： Inactivation of the p53 pathway and overexpression of HPV16/ 18-E6 and MDM2 may contribute to the genesis of human laryngeal cell carcinoma.