宫颈上皮内瘤变p16、p53、Ki-67的表达与高危型HPV感染及其临床意义  

Association of p16,p53,Ki-67 expressions with high-risk human papilloma virus infection in cervical intraepithelial neoplasia

作　　者：史健[1] 郑军生[2] 尹方[3] 胡维维[1] 黄小军[1] 周小丽[1] 

机构地区：[1]广东省佛山市第一人民医院病理科,广东佛山528000 [2]中山大学第三医院妇产科,广东广州510630 [3]广东省佛山市第一人民医院妇产科,广东佛山528000

出　　处：《南方医科大学学报》2007年第4期515-517,共3页Journal of Southern Medical University

基　　金：佛山市卫生局科研立项课题(2004080);广东省科技计划项目(2004B31201008)

摘　　要：目的研究p16、p53、Ki-67在宫颈上皮内瘤变(CIN)中的表达,探讨其与高危型HPV感染的关系及临床意义。方法利用自制组织芯片对243例CIN病变上皮和30例正常上皮行免疫组化染色检测p16、p53及Ki-67表达情况,部分CIN病例用基因杂交捕获法检测高危型HPV感染情况。结果正常鳞状上皮与腺上皮p16、Ki-67和p53染色均为阴性,而在CIN中三者均有较高表达,且随CIN级别升高而表达增强,各组间有差别并与CIN分级呈正相关(P<0.001)。同时二者阳性表达均见分层现象,在CIN1中大部分阳性细胞局限于宫颈鳞状上皮的下1/3,在CIN2中累及上皮下2/3,而CIN3则多超过上皮的下2/3或全层弥漫阳性,各组间有差别且与CIN分级呈正相关(P<0.001)。p53的阳性率及表达强度从CIN1到CIN3逐渐增加,多组之间及CIN1与CIN2比较有差别且与CIN分级呈正相关(P<0.001),但CIN2与CIN3之间无差别。部分CIN1、CIN2及CIN3患者高危型HPV-DNA阳性率分别为37/52(71.2%)、50/58(86.2%)和50/55(90.9%),DNA相对含量多组之间及CIN1与CIN2比较有差别并与CIN分级呈正相关(P<0.001),CIN2与CIN3之间无差别。结论高危型HPV感染及p16、Ki-67及p53与宫颈癌前病变发生机制及病变进展相关,而联合检测p16蛋白和Ki-67抗原表达可作为CIN分级诊断的辅助方法,有较好的应用价值。Objective To investigate the association between p 16, p53 and Ki-67 expression and high-risk human papilloma virus （HPV） infection in cervical intraepithelial neoplasia （C/N）. Methods Using a self-prepared tissue microarray, p16, p53, and Ki-67 expression was detected in 243 cases of CIN and 30 cases of normal cervical epitheliums by immunohistochemistry, and high-risk HPV infection was detected by gene hybridization capture Ⅱ. Results p 16, p53 and Ki-67 expressions were all negative in normal cervical epitheliums, but all positive in CIN. The expression ofpl6 and Ki-67 was 88.2%（67/76）and 92.1% （70/76）in CIN grade 1, respectively, and both were 100% in CIN grades 2 and 3, and the intensity of positive expression was significantly correlated with CIN grade （P〈0.001）. The positive cells in CIN grade 1 were mostly within the lower 1/3 of the squamous epithelium, while in CIN grade 2, the positive cells involved the lower 2/3 of the epithelium layers; in CIN grade 3, more than 2/3 or almost the full thickness of the epithelium was involved, suggesting significant correlation between the involvement and CIN grades （P〈0.001）, p53 expression was positive in 31.6% （24/76） of the cases in CIN grade 1, 53.4% （47/88） in CIN grade 2 and 58.2% （46/79） in C/N grade 3, and the intensity of positive expression was in significantly correlation with CIN grades （P〈0.001）, but no significant difference occurred between CIN 2 and CIN 3. High-risk HPV were detected in 37/52 （71.2%） of the cases in CIN grade 1, 50/58 （86.2%） in CIN 2 and 50/55 （90.9%） in CIN 3, and the relative DNA amount was significantly correlated with CIN grade （P〈0.001）, but there as no significant difference between CIN 2 and CIN 3. Conclusions High-risk HPV infection and p16, p53, Ki-67 overexpression all play important roles in the carcinogenesis of cervical precancerous lesion, and both p16 and Ki-67 expression are useful markers in diagnosis and staging of CIN.

关 键 词：宫颈上皮内瘤变 P16 P53 KI-67 HPV 免疫组织化学 

分 类 号：R737.33[医药卫生—肿瘤]