宫颈鳞癌中癌基因C-myc与相关蛋白E_2F-1P15~(INK4b)的表达及临床意义的研究

目的探讨宫颈鳞状细胞癌癌变过程中C-myc基因与其相关蛋白E2F-1、P15INK4b的表达以及与宫颈鳞癌临床病理特征的相关性。方法选取60份宫颈鳞癌、61份宫颈上皮内瘤变(CIN)组织(其中CINⅠ～Ⅱ级31份,CINⅢ级30份)和21份正常宫颈组织。所有病例制成组织芯片,采用原位杂交技术检测各组宫颈病变中C-mycmRNA的表达情况;免疫组织化学法(Elivison二步法)检测各组中E2F-1、P15INK4b蛋白的表达。统计学方法采用χ2检验和Spearman等级相关分析。结果随着宫颈从正常组织到发生CINⅠ～Ⅱ、CINⅢ直至发展为鳞状细胞癌,C-mycmRNA、E2F-1和P15INK4b蛋白的阳性表达率显著增高,差异有统计学意义(P<0.05)。C-mycmRNA在2组间的表达差异均有统计学意义。E2F-1蛋白的阳性表达在CINⅢ与宫颈鳞癌组之间差异有统计学意义。P15INK4b蛋白的阳性表达在CINⅠ～Ⅱ与CINⅢ、CINⅢ与鳞癌组间比较差异有统计学意义(P<0.05)。C-mycmRNA与E2F-1、P15INK4b的阳性表达均呈正相关(P<0.01)。E2F-1与P15INK4b的阳性表达呈正相关(P<0.01)。结论 C-myc癌基因在子宫颈鳞状细胞癌的发生、发展过程中起重要作用,其高表达预示子宫颈鳞状细胞的不良转化。C-myc癌基因与E2F-1、P15INK4b蛋白共同作用于CINⅢ向浸润性鳞癌的发展过程。

The expressions of C-myc and associated proteins of E2F-1 and P15INK4b in cervical squamous carcinoma and its clinical signficance

Objective To explore the expressions of C-myc and associated proteins of E2F-1 and P15INK4b in cervical squamous carcinoma and their correlations with clinical pathological features of cervical squamous carcinoma. Methods Sixty cases of cervical squamous carcinoma, 61 cases of cervical intraepithelial neoplasia （CIN） （CIN Ⅰ-Ⅱ： n=31, CIN Ⅲ：n=30） and 21 cases of normal cervical tissue were selected. All cases were prepared into tissue chips, the expression of C-myc mRNA in cervical lesions in every group was detected by in situ hybridization （ISH） and expressions of E2F-1 ,P15INK4b by immunohistochemistry （Elivison two step method）. X2 test and Spearman＇s corre- lation were used for statistical analysis. Results Along with the development from the normal cervical tissue to CIN Ⅰ-Ⅱ, CIN Ⅲ and to squamous-cell carcinoma, the positive expression rates of C-myc mRNA, E2F-1 and P15INK4b protein were significantly increased （P〈0.05）. The expression of C-myc mRNA was found different between the two groups. The positive expression of E2F-1 protein was significantly different only in CINⅢ group and cervical squamous carcinoma group. The positive expression of P15INK4b protein showed differences between GIN Ⅰ- Ⅱ and CIN Ⅲ, and between CIN Ⅲ and squamous carcinoma group （P〈0.05）. The C-myc was positively correlated with the positive expressions of mRNA, E2F-I and P15INK4b （P〈0.01）. E2F-1 was positively correlated with the positive expression of P15INK4b （P〈0.01）. Conclusion C-myc oncogene played an important role in the occurrence and development process of cervical squamous carcinoma and its high expression indicated the adverse transformation of squamous cells. Further- more, C-myc oncogene might affect the development process of CIN Ⅲ to invasive squamous carcinoma together with E2F-1 and P15INK4b protein.