Ki-67和p16表达与宫颈上皮内瘤变发生发展相关性的探讨

Expressions of Ki-67 and p16 in the development of cervical intraepithelial neoplasia and cervical squamouse cell carcinoma

目的 观察Ki-67和p16在宫颈上皮内瘤变(CIN)中的分布特点及其与HPV16感染的关系,并探讨两者表达的意义.方法 采用免疫组织化学方法(EnVison两步法)检测Ki-67和p16在CINⅠ48例、CINⅡ52例、CINⅢ 40例和浸润性子宫颈鳞状细胞癌(SCC)36例中的表达情况.另选取正常子宫颈鳞状上皮20例作为对照组.结果 ①p16在正常子宫颈鳞状上皮表达均阴性(0/20),在CINⅠ、CINⅡ、CINⅢ和浸润性SCC中的阳性率分别为47.9%(23/48)、82.7%(43/52)、95.0%(38/40)、97.2%(35/36),与正常对照组相比差异均有统计学意义(χ2＝28.3812, P<0.01).p16阳性强度在各级CIN病变中不同,差异有统计学意义(χ2＝30.0869,P<0.01).②Ki-67在正常对照组有5例表达,在CINⅠ中的阳性率为66.7%(32/48),而100%的CINⅡ和CINⅢ均为Ki-67阳性(χ2＝28.3812, P<0.01).Ki-67阳性强度在各级CIN病变中不同(χ2＝30.0869,P<0.01).③HPV16在正常组均为阴性,在33.3%(16/48)CINⅠ级、48.1%(25/52)CINⅡ级、87.5%(35/40)CINⅢ级、91.7%(33/36)子宫颈浸润性鳞状细胞癌中为阳性.HPV16感染与p16表达呈正相关(r=0.33,P<0.05),而与Ki-67表达无相关性(P>0.05).结论 p16在各级CIN中呈现不同的分布特点并与HPV16感染有关,是子宫颈CIN病变中细胞异型程度高的标记物.p16和Ki-67的高表达与CIN发生发展及最终癌变有密切关系.

Objective To investigate the expression of p16 and Ki-67 in cervical intraepithelial neoplasia and cervical squamous cell carcinoma and the relationship with HPV16 infection.Methods Immunohistochemical study for p16 and Ki-67 and HPV16 were performed on paraffin-embedded tissue of diagnostic biopsies and surgical materials, including 20 normal cervix, 48 CINⅠ, 52 CINⅡ,40 CINⅢ and 36 invasive cervical SCC.Results ①There was no p16 positive cell in normal control samples. Overexpression of p16 was detectedin samples of CINⅠ,CINⅡ,CINⅢ and SCC at frequencies of 47.9%(23/48),82.7%(43/52),38/40(95.0%) and 97.2%(35/36). There was significant statistic difference in these groups(χ2＝28.3812, P<0.01). ②Overexpression of Ki-67 were also detectedin samples of CIN at frequencies of 66.7%(32/48) in CINⅠand 100% in CINⅡ/Ⅲ(χ2=30.0869,P<0.01). ③HPV16 was showed negative in normal control group. However, 33.3%(16/48)CINⅠ,48.1%(25/52)CINⅡ,87.5%(35/40)CINⅢand 91.7%(33/36) cervical SCC were HPV16 positive. Overexpression of p16 was correlated with HPV16 infection(r=0.33,P<0.05). However not was Ki-67 (P>0.05). Conclusions Overexpression of the protein p16 is atypical marker for dysplastic and neoplastic epithelium of cervixuteri, which is associated with HPV16 infection.