P16、Ki67和MCM5在宫颈上皮内瘤变中的表达及意义

Expression of P16,Ki67 and MCM5 in cervical intraepithelial neoplasia and their prognostic significance

目的探讨P16、Ki67、MCM5蛋白在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)中的表达特征,与CIN分级和高危HPV感染的关系,及其提示CIN预后的意义。方法选取组织学诊断为CIN181例(其中CINⅠ54例,CINⅡ87例,CINⅢ40例),荧光PCR方法检测病变中高危HPV(HPV16/18/31/33/35/39/45/51/52/56/58/59/68)的感染情况;以非宫颈病变切除的子宫颈组织为正常对照,免疫组织化学EnVison法检测P16、Ki67和MCM5在宫颈CIN中表达情况;对患者进行随访,观察这些指标的表达与CIN临床病理特征关系以及其对CIN病变预后的意义。结果 (1)CIN病变中高危HPV阳性率为63.54%(115/181),在各级CIN中阳性率分别为:CINⅠ33.3%(18/54),CINⅡ73.56%(64/87)和CINⅢ82.5%(33/40),其差别有统计学意义。(2)P16在各级CIN病变中的阳性率分别为42.6%(23/54)、85.1%(74/87)和87.5%(35/40),并呈现不同的分布特征;Ki67在各级CIN病变中的阳性率分别为68.5%(37/54)、63.2%(55/87)和60%(24/40);两者的表达与CIN分级有关。MCM5在各级CIN病变中的阳性率分别为68.5%(37/54)、67.8%(59/87)和77.5%(31/40),其表达差别有统计学意义,但与CIN分级无关。(3)对其中86例患者进行1～126个月时间的随访,60患者经过锥切或者LEEP术治疗,其中35例病变持续存在或进展为高级别病变;而26患者未经治疗,其中14例患者病变持续存在或进展为高级别病变,2例发展为浸润癌。Ki67和MCM5表达与CIN病变的预后有提示作用。结论 P16,MCM5和ki67表达均与高危HPV感染有关,三者在不同级别CIN中表达率不同,有助于CIN的诊断,P16的不同分布特征与CIN病变级别有关;而MCM5的表达与P16和ki67一致,是有助于CIN诊断的有效标记物;ki67和MCM5表达能提示CIN的不良预后。

Objective To investigate the expression of P16,Ki67 and MCM5 in cervical intraepithelial neoplasia（CIN） and its relation to disease prognosis.Methods Tissue samples were collected from 181 CIN patients,including 54 cases of CIN,78 CIN II and 40 CIN I.Fluorescence PCR was used to detect high risk human papillovirus（HR-HPV） infection（HPV16/18/31/33/35/39/45/51/52/56/58/ 59/68）.Tissue sections were stained for three biological markers,P16,ki67 and MCM5 by immunohistochemstry EnVision method.Results HR-HPV infection was detected in 115 cases,18 case（33.3%） of CTN,64 cases（73.56%） of CINⅡand 33 cases（82.5%） of CINⅢ.P16 was over-expressed in 23 cases（42.6%） of CIN,74 cases（85.1%） of CINⅡand 35 cases（87.5%） of CINⅢ.Ki67 was over-expressed in 37 cases（68.52%） of CTN,55 cases（63.2%） of CTNⅡand 24 cases（60.0%） of CTINⅢ.PI6 and ki67 expressions were correlated with CTN grade.MCM5 was over-expressed in 37 cases（68.5%） of CTNⅠ,59 cases（67.8%） of CTNⅡand 3leases（77.5%） of CINⅢ,which was not related to CIN grade.Eighty six patients were followed up for 1-126 months. Sixty patients were treated by loop electrosurgical excision procedure（LEEP） or conization of cervix; diseases were persistent or progressed in 35 cases.Twenty six patients were not treated and CIN was persistent or progressed in 14 cases,including 2 cases progressing to invasive squamous carcinoma. High expression of Ki67 and MCM5 were related to CIN persistent or progress.Conclusions Expression of P16,Ki67 and MCM5 is correlated with HR-HPV infection.The expression of MCM5,PI 6 and Ki67 can be used as biomarkers for CIN.Both Ki67 and MCM5 expression may indicate the risk for progress of cervical intraepithelial neoplasia.