p21^(WAF1/Cip1)和p27^(Kip1)在宫颈癌及癌前病变的表达及临床意义

The clinical study on p21^(WAF1/Cip1) and p27^(Kip1) expression in cervical carcinoma and intraepithelial neoplasia

目的:探讨细胞周期负向调控因子p21WAF1/Cip1和p27Kip1在宫颈癌及癌前病变(CIN)中的表达特点。方法:选择妇科门诊宫颈疾病专科就诊患者163例,用第二代杂交捕获试验(HCⅡ)检测高危型人乳头瘤病毒(HR-HPV)DNA负荷量,阴道镜下宫颈活检,病理确诊,并用活检组织行p21WAF1/Cip1和p27Kip1免疫组化检测,比较慢性宫颈炎、CINⅠ-Ⅲ及宫颈癌各组间HR-HPV负荷量和p21WAF1/Cip1、p27Kip1表达差异。结果:各病理类型病变(共5组)的HR-HPV阳性率分别为:慢性宫颈炎38.46%(15/39),CINⅠ80%(12/15),CINⅡ81.82%(18/22),CINⅢ93.33%(56/60),宫颈鳞癌88.89%(24/27)。慢性宫颈炎HR-HPV DNA负荷量明显低于其他4组(M=0.56pg/ml,P<0.01),CINⅠ~Ⅲ及宫颈癌4组间无显著差异(P>0.05)。p21WAF1/Cip1和p27Kip1阳性表达率在CINⅠ~Ⅲ及宫颈癌4组间无显著差异(CINⅠ40.00%、60.00%,CINⅡ54.55%、54.55%,CINⅢ56.67%、70.00%,宫颈癌51.85%、77.78%,P>0.05),但均显著高于慢性宫颈炎组(5.13%、17.95%,P<0.01);p21WAF1/Cip1和p27Kip1表达增强与HR-HPV DNA负荷量升高和宫颈病变进展呈正相关,相关系数(rs)分别为:p21WAF1/Cip1:0.27、0.34,P<0.01;p27Kip1:0.30、0.46,P<0.01。结论:p21WAF1/Cip1和p27Kip1表达增强与宫颈病变进展密切相关,对宫颈HR-HPV持续感染及高负荷量患者可行p21WAF1/Cip1和p27Kip1检测以预测细胞病变的发生和发展。

Objective： To investigate expression alteration of cell cycle regulators p21^WAF1/Cip1 and p27^Kip1 in cervical cancer and its precursor lesions（CIN）. Methods ：The retrospective study was carried out in which 163 women for cervical lesion treatment were recruited. HR-HPV DNA was determined by hybrid capture Ⅱ （ HC Ⅱ）, and cervical biopsy was obtained under colposcopy with final diagnoses by histopathologic tests. Then p21^WAF1/Cip1 and p27^Kip1 expressions were detected by immunohistochemical tests. Results：HR-HPV DNA was detected in different cervical diseases and the infection rates were the following：chronic cervicitis 38.46% （15/39） ,CINⅠ 80% （12/15） ,CIN Ⅱ 81.82% （18/22） ,CINⅢ93.33% （56/60） ,cervical squamous cell carcinoma 88.89% （24/27）. Significant difference existed in HR-HPV DNA load between chronic cervicitis（ M = 0.56pg/ml, P 〈 0.01 ）and CIN Ⅰ -Ⅲ, cervical squamous cell carcinoma, but there was no significance among the latter. Positive expression rates of p21^WAF1/Cip1 and p27^Kip1were 5.13%, 17.95% in chronic cervicitis,40.00% ,60.00% in CINⅠ ,54.55% ,54.55% in CIN Ⅱ ,56.67% ,70.00 % in CINⅢ ,and 51.85% ,77.78% in cervical squamous cell carcinoma. Significant difference was found between chronic cervicitis and the other 4 groups,while no significance was showed among the 4 groups（P 〈0.01 ）. There existed correlation between elevated p21^WAF1/Cip1, p27Kipq expressions and increased HR-HPV DNA load（ rs：0. 27,0.30,P 〈0.01 ） ,aggravated cervical diseases （ rs：0. 34,0.46 ,P 〈0.01 ）. Conclusions： High HR-HPV DNA load is a risk factor for occurrence of cervical cancer and its precursor leasions. Positive p21^WAF1/Cip1 and p27^Kip1expression are biomarkers of development and aggravation of cervical diseases.