【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。更多还原

【Abstract】 Objective To investigate the association between p16, p53 and Ki-67 expression and high-risk human papilloma virus (HPV) infection in cervical intraepithelial neoplasia (CIN). 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 p16, p53 and Ki-67 expressions were all negative in normal cervical epitheliums, but all positive in CIN. The expression of p16 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 CIN 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.更多还原