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HPV16/18-E6、p53和MDM2蛋白在人喉鳞癌中的表达及相关性研究
强笔,马纪清,邱杰,何金,赵舒薇,郎军添,叶青,王海青
0
(第二军医大学长征医院耳鼻咽喉科,上海 ,200003)
摘要:
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%(l/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%(l/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)。HPV16/18-E6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。
关键词:  喉肿瘤  癌,鳞状细胞  乳头状瘤病毒, 人  E6蛋白  p53蛋白  MDM2蛋白
DOI:10.3724/SP.J.1008.2006.01320
基金项目:
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
()
Abstract:
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%(l/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%(l/15), 37.5%(9/24), and 70.8%(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.
Key words:  laryngeal neoplasms  carcinoma, squamous cell  papillomavirus,human  E6 protein  p53 protein  MDM2 protein?