子宫颈鳞状细胞癌人类乳头状瘤病毒16／18、p16及Her-2的表达及其临床意义

Expression and clinical significance of HPV16/18, p16, Her-2 in squamous cell cervical carcinoma

目的研究子宫颈鳞状细胞癌癌变过程中高危型人类乳头状瘤病毒（HPV）、p16及Her-2的表达及临床意义。方法利用组织芯片技术结合显色原位杂交、免疫组织化学和荧光原位杂交（FISH）技术检测60例子宫颈鳞状细胞癌、61例子宫颈上皮内瘤变（CIN）以及21例正常子宫颈组织中HPV16／18、p16及Her．2的表达及Her-2基因扩增的情况。结果在正常子宫颈组、CINI-Ⅱ组、CIN III组、子宫颈鳞状细胞癌组中，HPV16／18和p16的阳性率均逐渐升高，分别为0（0／21）、9．68％（3／31）、46．67％（14／30）、71．67％（43／60）；0（0／21）、19.35％（6／31）、93.33％（28／30）、96．67％（58／60），HPV16／18除正常组子宫颈组与CINI-Ⅱ组间、p16除CIN III组与子宫颈鳞状细胞癌组间的差异无统计学意义（P〉0．05），其余各组阳性率差异均有统计学意义（P〈0．05）；Her-2表达的阳性率在CINⅢ组与子宫颈鳞状细胞癌组分别为13．33％（4／30）和31．67％（19／60），Her-2基因扩增率分别为3．33％（1／30）和21．67％（13／60），正常子宫颈组与CINI-Ⅱ组Her-2阳性率和Her-2基因扩增率均为0，子宫颈鳞状细胞癌组与CIN组、正常子宫颈组比较，差异有统计学意义（P〈0．05）。Her-2蛋白表达及Her-2基因扩增与子宫颈鳞状细胞癌的分化程度、分期及淋巴结转移呈正相关（P〈0．05）。结论HPV感染是子宫颈鳞状细胞癌发生的触发因素之一；p16蛋白的表达与Her-2基因的扩增可能参与调控了子宫颈鳞状细胞癌的发生、发展过程，其高表达预示子宫颈鳞状细胞癌的不良预后。

Objective To study the expression of HPV,pl6 and Her-2 in the squamous cell cervical carcinoma and its clinical significance. Methods Expression of HPV16/18,p16, and C-erbB-2 and the amplification of Her-2 gene were examined using situ hybridization technique, SP immunohistochemistry, and FISH imaging analysis system in 60 cases of cervical cancer, 61 cases of CIN, and 21 cases of normal cervical tissue, respectively. Results The positive rates of HPV16/18 and p16 in the normal tissue, CIN I -II, CIN III and the squamous cell cervical carcinoma were gradually increased, they wereo （0/21）,9.68 % （3/31）, 46.67 % （14/30）, 71.67 % （43/60）;0 （0/21）, 19.35 % （6/31）, 93.33 % （28/30）,96.67 % （58/60）,respectively, and there were significant differences among the groups （P〈0.05）,but no significant difference was found between the normal tissue and the CIN I - II. The positive rates of Her-2 and Her-2 in the CIN Ill and the carcinoma were 13.33 % （4/30）,31.67 % （19/60）, 3.33 % （1/30）,21.67 % （13/60）, respectively, but in the normal group and the CIN I -1I wereo, and the differences between the carcinoma group and the CIN group, the carcinoma group and the normal group were significant（P〈0.05）. The expression of Her-2 and the amplification of Her-2 were closely related to the stage, degree of differentiation and metastasis of lymph node in the squamous cell cervical carcinoma （P〈0.05）. Conclusion The infection of HPV is one of the triggers for the squamous cell cervical carcinoma. The expression of pl6 and the amplification of Her-2 may be closely correlated with tumor development and high expression of pl6 and Her-2 indicates poor prognosis.