不同宫颈组织中PIK3CA、PTEN和p16蛋白表达及其与HPV16/18感染的关系

 目的 探讨PIK3CA、PTEN和p16蛋白在人正常宫颈上皮、宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN） 和宫颈鳞癌组织中的表达，以及PIK3CA、PTEN和p16蛋白表达与人乳头瘤病毒（human papillomavirus，HPV）感染 之间的关系。方法采用免疫组织化学二步法在22例健康者宫颈组织、72例宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）和30例宫颈鳞癌组织中检测PIK3CA、PTEN和p16蛋白的表达，显色原位杂交方 法检测高危型HPV16/18的感染。结果PIK3CA和p16蛋白表达阳性率和HPV16/18的感染率均随着宫颈上皮逐渐恶变而 上升，PTEN蛋白表达却 呈现相反的结果。PIK3CA、PTEN、p16蛋白和 HPV16/18的感染率在宫颈鳞癌和CIN Ⅱ～Ⅲ组中的表达分别与对照组和CIN Ⅰ组相比，差异均有统计学意义（P＜ 0.05）。在宫颈上皮内瘤变组织中，39例（76.47%）CIN Ⅱ～Ⅲ 中显示PIK3CA阳性，仅有9例 （42.86%）CIN Ⅰ中显示 PIK3CA阳性，两组间差异有统计学意义（P=0.006），而PTEN和p16蛋白在宫颈上皮内瘤 变不同组别中相比差异均无统计学意义。在81例CIN Ⅱ～Ⅲ和鳞癌组织中，PIK3CA和p16蛋白呈显著正相关关系 （P=0.000，r=0.544）。PIK3CA、p16蛋白与PTEN蛋白表达之间，两者均呈显著负相关（P＜0.05）。 HPV16/18阳性的47例标本中，PIK3CA和p16蛋白几乎均呈阳性表达，呈显著正相关（P<0.01），但PTEN蛋白却有37例呈阴性表达，无显著相关（P=0.116）。结论PIK3CA、PTEN、p16蛋白表达以及高危型HPV感染与宫颈癌的发生发展均密切相关。PIK3CA、PTEN、p16蛋白和高危型HPV感染联合检测，可作为宫颈癌早期癌变的分子标志物。高危型HPV感染可能有助于PIK3CA和p16蛋白的高表达。

Correlation between PIK3CA,PTEN and p16 Protein Expression and Human Papillomavirus Infection in Different Cervical Tissues

Objective To evaluate correlations between PIK3CA,PTEN and p16 protein expression,and human papillomavirus(HPV) infection in the normal cervix epithelium,cervical intraepithelial neoplasia(CIN) and cervix squamous cell carcinoma(SCC).Methods The immunohistochemical staining PV-9000 method was used to detect the expression of PIK3CA,PTEN and p16 protein and high-risk HPV16/18 infection was detected by chromogenic in situ Hybridization in 30 cases of SCC(SCC group),21 cases of CIN Ⅰ(CINⅠgroup),51 cases of CINⅡ～Ⅲ(CIN Ⅱ～Ⅲ group),and 22 cases of normal cervix tissues(control group).Results PIK3CA and p16 protein expression rate and HPV16/18 infection rate were gradually increased,but PTEN protein expression rate was gradually decreased along with the malignant transformation of cervical epithelium.The differences of PIK3CA,PTEN,p16 protein and HPV16/18 prevalence in cervical cancer and CIN Ⅱ ~ Ⅲ group were significant,compared with control group or CIN Ⅰ group,(P<0.05).In cervical intraepithelial neoplasia tissues,PIK3CA positive rate(76.47%,39 cases) in CIN Ⅱ ~ Ⅲwas significant higher than that in CIN Ⅰ(42.86%,9 cases),P=0.006.PTEN and p16 protein positive rates were similar in different CIN groups.In 81 cases of human CIN Ⅱ ~ Ⅲ and squamous cell carcinoma,PIK3CA showed a significant positive correlation to p16 protein(P=0.000,r=0.544).PIK3CA,p16 protein were negative correlated to PTEN protein expression(P<0.05).In 47 HPV16/18 positive specimens,PIK3CA,and p16 protein expressions almost were positive correlation(P<0.01),but 37 cases of PTEN protein expression were negative,(P=0.116).Conclusion PIK3CA,PTEN,p16 protein expression and high-risk HPV infection were closely related to the development of cervical cancer.Combined detection of PIK3CA,PTEN,p16 protein and high-risk HPV might be a molecular marker for SCC early diagnosis.The over-expressions of PIK3CA and p16 protein were related with high-risk human papillomavirus infection.