细胞衰老和凋亡相关蛋白表达在宫颈鳞癌变中的意义

Significance of Senescence and Apoptosis Associated Proteins Expression in Cervical Squamous Carcinogenesis

目的:许多细胞周期调控因子和衰老相关标志物如p14ARF、p15INK4b、p16INK4a和p53在G1细胞周期阻滞和癌基因诱导的衰老中意义重大。这些关键的调节蛋白在多种恶性肿瘤中经常发生突变或是缺失。在本研究中将探讨这些因子在宫颈癌发生中的意义。方法:在本研究中在正常宫颈上皮、宫颈上皮内瘤变和宫颈鳞癌中,应用免疫组织化学方法检测p14ARF、p15INK4b、p16INK4a、Bcl-2、p53表达,并分析它们的表达与宫颈癌变的相关性。结果:p16INK4a在正常宫颈鳞状上皮10%(2/20)表达阴性,在大部分CIN和宫颈鳞癌中表达阳性,其中在85%(17/20)CIN和75%(15/20)鳞癌中呈弥漫性强阳性表达,CIN和宫颈鳞癌中的阳性表达率显著高于正常上皮(P<0.01),CIN和宫颈鳞癌的间表达率无显著差异。p15INK4b在正常宫颈鳞状上皮中65%(13/20)表达弱阳性,在100%(20/20)CIN和95%(19/20)宫颈鳞癌中表达弥漫性阳性,各组之间阳性表达率无显著性差异(P>0.05)。p14ARF在40%(8/20)正常宫颈上皮细胞中表达呈弱阳性(1+),在宫颈鳞癌中表达呈弥漫性强阳性90%(18/20),在45%(9/20)CIN中表达阳性,各组之间阳性表达率无显著性差异(P>0.05)。Bcl-2在20%(4/20)正常宫颈上皮表达呈弱阳性,在18/20CIN中其表达强度和比率均增加,阳性表达率为90%(18/20),Bcl-2在鳞癌中700%(14/20)呈强阳性和弥漫阳性,CIN和宫颈鳞癌中的阳性表达率显著高于正常上皮(P<0.01),CIN和宫颈鳞癌的间表达率无显著差异。P53免疫组化染色显示在正常宫颈上皮为表达为20%(4/20),在大多数CIN25%(5/20)和鳞癌中核阳性85%(17/20),在鳞癌中的阳性表达率显著高于正常宫颈上皮和CIN病变(P<0.05)。结论:宫颈鳞癌变涉及包括细胞凋亡和细胞衰老在内的多种信号分子表达异常,这些分子可能在宫颈鳞癌发生发挥重要作用并在宫颈癌早期诊断中有重要意义。

Objective： Some cell cycle regulators and Senescence associated proteins, such as pl4ARF, pl51NK4b, pl6INK4a, p53 are important in G1 cell cycle arrest and oncogene-induced senescence. The genes of these key regulator proteins are often mutated or deleted in various malignancies. This study was to explore the significance of these factors in the pathogenesis of cervical carcinoma. Methods： Positivity rate of P 161NK4a in normal cervical squamous epithelium was 10% （2/20）, and 85% （17/20） CIN and 75% （15/20） in squamous cell carcinoma which showed diffuse strong positive expression. The positivity rate of P161NK4a in CIN and cervical squa- mous cell carcinoma was significantly higher than that of normal epithelium （P〈0.01）, and there was no significant difference between C1N and squamous cell carcinoma of the cervix. Positivity rate of P15INK4b in normal cervical squamous epithelium was 65% （13/20）, and 100% （20/20） in CIN and 95% （19/20） in cervical squamous cell carcinoma with diffuse positive expression, there was no significant difference of the positive expression rate between the groups （P〉0.05）. Positivity rate of P14ARF （8/20） was 40% in normal cervical ep- ithelial cells, and 90% （18/20） in cervical squamous cell carcinoma with diffuse strong positive expression, 45% （9/20） expression of CIN, and no significant difference of the positive expression rate between the groups （P〉0.05）. Positivity rate of Bcl-2 was 20% （4/20） in normal cervical epithelium, and 90% （18/20） in CIN, 70% （14/20） in squamous cell carcinoma with strongly positive and diffuse stain- ing, the positive rate of CIN and cervical squamous cell carcinoma was significantly higher than that in normal epithelium （P〈0.0I）, and there was no significant difference between CIN and cervical squamous cell carcinoma. P53 immunohistochemical staining showed that in normal cervical epithelial expression was 20% （4/20）, 25% （5/20） in CIN and 85% （17/20） in squamous cell carcinoma, the positive rate of CIN and cervical squamous cell carcinoma was significantly higher than that in normal epithelium （P〈0.05）. Conclusion： Squa-mous cell carcinoma of the uterine cervix was related to abnormal expression of many signal molecules including cell apoptosis and cell senescence, and played a significant role in cervical squamous cell carcinogenesis and early diagnosis for cervical carcinoma.