细胞周期素D1和抗原Ki-67在宫颈上皮内瘤样病变和宫颈鳞癌的表达及与人乳头瘤病毒感染转归的关系

Expressions of cyclin D1 and Ki-67 in cervical intraepithelial neoplasia and squamous cell carcinoma of cervix as related to prognosis of human pappilloma virus infection

目的 研究细胞周期素D1（cyclin D1）、抗原Ki-67在宫颈上皮内瘤样病变（CIN）和宫颈鳞癌发生发展中作用及其与人乳头瘤病毒（HPV）感染转归的关系.方法 2002年1月至2006年12月广州医学院第一附属医院HPV阳性患者104例,分2组：（1）研究组：82例,即病理确诊CIN Ⅰ组17例、CINⅡ组19例、CINⅢ组23例、宫颈鳞癌组23例.（2）对照组：柱状上皮异位22例.应用EnVision法检测宫颈病变组织中cyclin D1、Ki-67蛋白的表达,杂交捕获试验检测宫颈分泌物或阴道残端中HPV感染情况,随访各组患者术后1年内的HPV变化.结果 （1）cyclin D1在各组宫颈组织细胞核内均有表达.其阳性率CINⅢ组[82.61%（19/23）]、宫颈鳞癌组[86.96%（20/23）]与对照组[27.27%（6/22）]、CINⅠ组[58.82%（10/17）]比较,差异有统计学意义（P〈0.05）,在宫颈鳞癌组与CINⅡ组[68.42%（13/19）]阳性率比较差异有统计学意义（P〈0.05）.（2）Ki-67在各组宫颈组织细胞核内均有表达,其对照组阳性率[31.82%（7/22）]与CINⅢ组[86.96%（20/23）]、宫颈鳞癌组[91.30%（21/23）]比较差异有统计学意义（P〈0.05）,而在宫颈鳞癌组与CINⅠ组[58.82%（10/17）]、CIN Ⅱ组[63.16%（12/19）]比较差异有统计学意义（P〈0.05）.（3）术后1年内各组HPV的转阴率分别与cyclin D1、Ki-67的表达强度呈负相关（rs=-0.299,rs=-0.367,P〈0.05）.结论 cyclinD1和Ki-67在CIN和宫颈鳞癌的细胞增殖活动中起作用,且两者可能与HPV感染转阴率有关.

Objective To investigate the expressions of cell cycle protein D1 （cyclin D1） and proliferation cell nuclear antigen （Ki-67） in cervical intraepithelial neoplasia （CIN） and squamous cell carcinoma （SCC） of cervix as related to prognosis of HPV infection. Methods Between January 2002 and December 2006,104 patients with positive human pappilloma virus （HPV） in The First Affiliated Hospital of Guangzhou Medical College were divided into two groups：the study group （n=82） comprising 17 cases of CIN Ⅰ,19 of CIN Ⅱ,23 of CIN Ⅲ and 23 of SCC （all confirmed by pathology）,and the control group comprising 22 cases of cylindrical epithelium dystopia. Immnunohistochemical En Vision assay was used to detect the expressions of cyclin D1 and Ki-67,and hybird capture Ⅱ was used to detect HPV,in cervical discharge or virginal stump. All the patients were followed up for status of HPV within one year after operation. Results Expression of cyclin D1 was found in nuclei of cervical tissue cells of all the groups,including 82.61% （19/23） of CIN Ⅲ lesions and 86.96% （20/23） of SCC,compared significantly with 27.27%（6/22） of cylindrical epithelium dystopia and 58.82% （10/17） of CIN Ⅰ （P〈0.05）. More cyclin D1was expressed in SCC than that in CIN Ⅱ （P〈0.05）. Expression of Ki-67 was found in nuclei of cervical tissue cells of all the groups,including 86.96%（20/23） of CIN Ⅲ and 91.30% （21/23） of SCC compared significantly with 31.82% （7/22） of cylindrical epithelium dystopia （P〈0.05）. The rate of Ki-67 expression in SCC also compared significantly with that in CIN Ⅰ[58.82%（10/17）]and in CIN Ⅱ[63.16% （12/19）]（P〈0.05）. Within one year after operation,the conversion of HPV was negatively correlated with level of cyclin D1 or Ki-67 expression （rs=-0.299,rs=-0.367,P〈0.05）. Conclusion cyclin D1 and Ki-67 may have a role in the proliferation of CIN and SCC cells,and in HPV conversion.