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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。
PURPOSE: Many of the cell cycle regulators and age-related markers such as p14ARF, p15INK4b, p16INK4a and p53 are important in G1 cell cycle arrest and oncogene-induced senescence. These key regulatory proteins are often mutated or deleted in a variety of malignancies. In this study, we will explore the significance of these factors in the development of cervical cancer. Methods: The expressions of p14ARF, p15INK4b, p16INK4a, Bcl-2 and p53 were detected by immunohistochemistry in normal cervical epithelium, cervical intraepithelial neoplasia and cervical squamous cell carcinoma in this study. The expression of p14ARF, p16INK4a, Correlation. RESULTS: p16INK4a was negative in 10% (2/20) of normal cervical squamous epithelium and positive in most CIN and cervical squamous carcinomas, with 85% (17/20) CIN and 75% (15/20) squamous cell carcinoma The positive expression rate in CIN and cervical squamous cell carcinoma was significantly higher than that in normal epithelium (P <0.01). There was no significant difference between CIN and cervical squamous cell carcinoma. p15INK4b expressed weakly positive in 65% (13/20) of normal cervical squamous epithelium, diffusely positive in 100% (20/20) CIN and 95% (19/20) cervical squamous cell carcinoma, positive between the groups There was no significant difference in the expression rate (P> 0.05). The expression of p14 ARF was weakly positive in 40% (8/20) of normal cervical epithelial cells (1+). The expression of p14ARF was strongly diffuse in 90% (18/20) of cervical squamous cell carcinomas and in 45% (9/20) CIN positive expression, positive expression rate between the groups no significant difference (P> 0.05). The expression of Bcl-2 was weakly positive in 20% (4/20) of normal cervical epithelium, and the expression of Bcl-2 was up-regulated in 18 of 20 CIN. The positive expression rate of Bcl-2 was 90% (18/20) The positive expression rate in CIN and cervical squamous cell carcinoma was significantly higher than that in normal epithelium (P <0.01). There was no significant difference between CIN and cervical squamous cell carcinoma. P53 immunohistochemical staining showed 20% (4/20) expression in normal cervical epithelium, 85% (17/20) positive in most CIN25% (5/20) and squamous cell carcinomas, positive in squamous cell carcinomas The expression rate was significantly higher than that of normal cervical epithelium and CIN (P <0.05). CONCLUSIONS: Cervical squamous cell carcinogenesis involves abnormal expression of various signaling molecules including apoptosis and cell senescence. These molecules may play an important role in the occurrence of cervical squamous cell carcinoma and have important significance in the early diagnosis of cervical cancer.