Aberrant expression of the cell cycle associated proteins TP53, MDM2, p21, p27, cdk4, cyclin D1, RB, and EGFR in cervical carcinomas

作     者：Skomedal, H Kristensen, GB Lie, AK Holm, R 

作者机构：Univ Oslo Norwegian Radium Hosp Dept Pathol Inst Canc Res N-0310 Oslo Norway Univ Oslo Norwegian Radium Hosp Dept Gynecol Oncol Inst Canc Res N-0310 Oslo Norway 

出 版 物：《GYNECOLOGIC ONCOLOGY》 (妇科肿瘤学)

年 卷 期：1999年第73卷第2期

页      面：223-228页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Kreftforeningen  NCS 

主　　题：细胞周期蛋白质类/遗传学 细胞周期蛋白D1/遗传学 细胞周期蛋白依赖激酶4 细胞周期蛋白质依赖激酶类/遗传学 基因表达调控 肿瘤/遗传学 微丝蛋白质类/遗传学 肌蛋白质类 肿瘤蛋白质类/遗传学 核蛋白质类 癌基因蛋白质p21(ras)/遗传学 原癌基因蛋白质类/遗传学 原癌基因蛋白质c-mdm2 受体 表皮生长因子/遗传学 视网膜母细胞瘤蛋白质/遗传学 肿瘤抑制蛋白质p53/遗传学 宫颈肿瘤/遗传学 成年人 老年人 老年人 80以上 女(雌)性 人类 中年人 

摘      要：Objective, The aims of this study were to study aberrant expression and coexpression of the cell cycle associated proteins TP53, p21, p27, cyclin D1, cdk4, RE, EGFR, and MDM2 in cervical carcinomas, to correlate protein alterations with histopathological and clinical parameters, and to evaluate whether these alterations provide prognostic information. Methods, Seventy-four cervical carcinomas and 10 cases of normal cervical epithelium from patients with benign uterine leiomyomas were investigated immunohistochemically for aberrant expression of the cell cycle associated proteins using the biotin-streptavidin-peroxidase method and the OptiMax Plus automated cell staining system, Results. In normal cervical epithelium p27 immunostaining was identified in more than 50% of the cells, cdk4 in 5-50% of the cells, and EGFR in less than 5% of the cells, whereas no immunostaining for TP53, p21, MDM2, or cyclin D1 was detected. Positive RE protein staining was identified in all cases of normal cervical epithelium. RE protein staining was also identified in all carcinomas of the cervix uteri. Overexpression of p21 was found in 96% of the tumors, MDM2 in 35%, cdk4 in 69%, cyclin D1 in 3%, and EGFR in 20% of the tumors. A low level of p27 was observed in 65% of the cases. In a previous study, the TP53 protein level has been found to be elevated in 41 of the 74 (55%) cases included in this work. Significant coexpression was seen for TP53 and MDM2 (P = 0.001);concording results were observed in 67% of the cases. There was no difference in aberrant expression or coexpression of any of the cell cycle regulatory proteins related to histological type, grade of differentiation, FIGO stage, or relapse-free survival. Conclusion. The high number of cases showing increased levels of p21 and cdk4 and decreased levels of p27 suggests that these proteins may be important in the pathogenesis of cervical carcinoma. Furthermore aberrant expression of MDM2 in a smaller but significant fraction of