宫颈上皮内瘤变及早期宫颈癌组织中P16、HPV L-1壳蛋白的表达及与HR-HPV载量相关性研究

Expression of P16 and Human Papillomavirus L-1 Caspid Protein in Cervical Intraepithelial Neoplasia and Early Cervical Carcinoma and Their Relationship to Viral Load of High-Risk Human Papillomavirus

目的：探讨宫颈上皮内瘤变（CIN）及早期宫颈癌组织中P16、HPV L-1壳蛋白的表达及与高危型人乳头瘤病毒（HR-HPV）载量的相关性。方法：分别采用免疫组化法和第二代杂交捕获法（hybrid captureⅡ,HC-2）检测26例慢性宫颈炎组织、83例低度鳞状上皮内病变（LSIL）（CINⅠ83例）、109例高度鳞状上皮内病变（HSIL）（CINⅡ49例,CINⅢ60例）、11例早期宫颈鳞癌组织中P16蛋白、HPV L-1壳蛋白的表达及HR-HPV载量,并分析其相关性。结果：1在宫颈癌前病变中随病变级别增高,HR-HPV阳性率增加,差异有统计学意义（P〈0.01）。各组织学分级中病毒载量分布差异有统计学意义,HSIL（44.95%）及早期宫颈癌组织（63.64%）中皆以低病毒载量（1~100 RLU/CO）为主。从慢性宫颈炎、LSIL、HSIL到早期宫颈癌,P16蛋白阳性表达率分别为11.54%（3/26）,55.42%（46/83）,85.32%（93/109）,100.00%（11/11）,差异有统计学意义（P〈0.01）;L-1壳蛋白阳性率分别为15.38%（4/26）,28.92%（24/83）,14.68%（16/109）,0.00%（0/11）,差异有统计学意义（P〈0.05）。2229例宫颈组织中,随HPV载量增加,P16蛋白表达增强;L-1壳蛋白阳性表达率增加,差异有统计学意义（P〈0.01）。3在慢性宫颈炎组中,P16蛋白阳性表达与HPV载量呈正相关（r=0.491,P〈0.05）。在LSIL组中,P16蛋白与HPV载量（r=0.459,P〈0.01）及L1壳蛋白表达（r=0.297,P〈0.01）皆呈正相关。4在HSIL及早期宫颈癌组中,P16蛋白、L-1壳蛋白表达与HPV载量三者之间无明显相关性（P〉0.05）。结论：P16、HPV L-1壳蛋白异常表达是宫颈癌前病变发生发展的早期分子事件,对判断CINⅠ有参考价值,可能比HR-HPV载量更具有预测价值。

Objective： To examine the expression of P16 and Human Papillomavirus（ HPV） L-1 caspid protein in cervical intraepithelial neoplasia（ CIN） and early cervical carcinoma and study the clinlic significance and relationship to viral load of High-risk（ HR） HPV. Methods： Expression of P16 and HPV L-1 caspid protein were detected by immunohistochemical staining in 26 cases of chronicl cervicitis,83 cases of Low-grade squamous intraepithelial lesion（ LSIL）,109 cases of high-grade squamous intraepithelial lesion（ HSIL）,and 11 cases of early cervical squamascarcinoma. All the patients received HR-HPV load detection by hybrid captureⅡ（ HC-2） before their surgical. Results： 1The positive rate of HR-HPV in CIN and early cervical carcinoma was significantly higher than that in chronic cervicitis（ P〈0. 01）. The expression level of P16 was 11. 54%（ 3 /26） in chronic cervicitis,55. 42%（ 46 /83） in LSIL,85. 32%（ 93 /109） in HSIL and 100. 00%（ 11 /11） in early cervical carcinoma,respectively,with significant differences（ P〈0. 01）. The positive staining of HPV L-1 caspid protein was 15. 38%（ 4 /26） in chronic cervicitis,28. 92%（ 24 /83） in LSIL,14. 68%（ 16 /109） in HSIL,0. 00%（ 0 /11） in early cervical carcinoma,respectively,with significant differences（ P〈0. 05）. 2The expression of P16 and HPV L-1 protein increased with the increasing of HR-HPV load in a total of 229 cases of cervical tissues（ P〈0. 01）. 3In the group of chronic cervicitis,the expression of P16 was positively correlated with the viral load of HR-HPV（ r = 0. 491,P 0. 05）. In the group of LSIL,the expression of P16 was positively correlated with the viral load of HR-HPV（ r = 0. 459,P〈0. 01）and the expression of HPV L-1（ r = 0. 297,P〈0. 01）. 4There was no relationship between the expression of P16,HPV L-1 caspid protein and HPV load in HSIL and early cervical squamascarcinoma.（ P〉0. 05）. Conclusions： The abnormal expression of P16 and HPV L-1 caspid protein was early molecular events in carcinogenesis and development of CIN and cervical carcinoma,possibly of greater value than HR-HPV in CINⅠ.