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

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

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 intraepitheli-al 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(humanpapillomavirus,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CINⅡ～Ⅲ组中的表达分别与对照组和CINⅠ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%)CINⅡ～Ⅲ中显示PIK3CA阳性,仅有9例(42.86%)CINⅠ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CINⅡ～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。

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,（P0.05）.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（P0.05）.In 47 HPV16/18 positive specimens,PIK3CA,and p16 protein expressions almost were positive correlation（P0.01）,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.