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

Objective, The aims of this study were to study aberrant expression and coe xpression of the cell cycle associated proteins TP53, p21, p27, cyclin D1, cdk4, RE, EGFR, and MDM2 in cervical carcinomas, to correlate protein alter ations with histopathological and clinical parameters, and to evaluate whet her these alterations provide prognostic information. Methods, Seventy-four cervical carcinomas and 10 cases of normal cervical e pithelium from patients with benign uterine leiomyomas were investigated im munohistochemically for aberrant expression of the cell cycle associated pr oteins 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 t han 5% of the cells, whereas no immunostaining for TP53, p21, MDM2, or cycl in D1 was detected. Positive RE protein staining was identified in all case s 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 pr evious 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 see n 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 cd k4 and decreased levels of p27 suggests that these proteins may be importan t in the pathogenesis of cervical carcinoma. Furthermore aberrant expressio n of MDM2 in a smaller but significant fraction of cases indicates that the se proteins could also be involved in the development of these cancers. Fin ally our results indicate that MDM2 may protect against HPV-induced TP53 pr otein degradation, (C) 1999 Academic Press.