细胞周期调控基因与人类乳头状瘤病毒在子宫颈癌中的表达

目的分析细胞周期调控基因p16^INK4A、细胞周期蛋白D1（Cyclin D1）及Ki-67蛋白与人乳头状瘤病毒（HPV）16／18、31／33在子宫颈鳞状细胞癌（ISCC）中的表达，研究其在ISCC发生、发展中的作用和相关性。方法应用组织芯片结合原位杂交法和免疫组织化学法检测66例ISCC、35例子宫颈上皮内瘤变（CIN）、30例正常子宫颈鳞状上皮（NCE）中p16^INK4A、Cyclin D1、Ki-67和HPV16／18、31／33的表达。应用SPSS13．0统计软件分析结果。结果HPV16／18、p16^INK4A、Cyclin D1及Ki-67在ISCC中的表达明显高于CIN和NCE组，差异有统计学意义；p16^INK4A蛋白阳性表达率与组织学分级呈正相关；Ki-67阳性表达率与淋巴结转移和子宫颈管壁浸润深度呈正相关；Cyclin D1蛋白与临床各参数均无相关性（P〉0．05）。结论高危HPV在ISCC的发生、发展中起重要作用，p16^INK4A基因可能不是单纯作为抑癌基因在子宫颈癌中起作用，Ki-67可以作为鉴别良、恶性肿瘤的有价值的临床参考指标。

Expression of p16INK4A, CyclinD1, Ki-67 and HPV infection in cervical squamous cell carcinoma

Objective To analyse the expression of p16INK4A, CyclinD1, Ki-67 proteins and HPV16/18, 31/33 in invasive squamous cell carcinoma of cervix(ISCC)and to indicate the significance of them in the occurrence and development of ISCC. Methods Using tissue microarray,in Situ Hybridization (ISH) and immunohistochemical method detected the expression of HPVI6/18, 31/33 and investigated the expression of p16INK4A, CyclinD1, Ki-67 in ISCC, CIN and NCE. Results was analysed by SPSS vision 13.0. Results The positive expression rate of HPV16/18, CyelinD1, Ki-67 in ISCC was markedly higher than that in CIN and NCE. Significant relationship was observed between p16INK4A protein expression and histological grade of the cancer. No significant correlation was observed between CyclinD1 protein expression and every clinical pathological parameters of ISCC. Conclusion High-risk HPV takes an important role in the development in ISCC. p16INK4A gene might not act as a suppressor-gene only on the occurrence in ISCC. Ki-67 can be looked as a valuable clinic index of diagnosing benign and malignant tumor.