Potential prognostic significance of apoptosis related oncogenes: p53, bcl-2 and mdm-2 in early stage cervical carcinoma

Abstract

Introduction: Evaluations of expression of apoptosis related oncogenes are being increasingly called upon in an attempt to better understand the carcinogenesis of cervical carcinoma and to provide possible prognostic information. The aim of this study was to analyze the expression of bcl-2, p53 and mdm-2 oncoproteins and cellular proliferative marker Ki-67 in early stage cervical carcinoma, with an emphasis on their association with human papillomavirus (HPV) infection, recurrence rate and lymph node status. Material and methods: Using immunohistochemistry, 69 radical hysterectomy specimens with cervical carcinoma (pT1b1/pT1b2) were studied. Evaluation of expression of p53, bcl-2, mdm-2 and Ki-67 was performed in surface area, center and invasion front of the neoplasms. The HPV presence was determined by CARD in situ hybridization. Results and conclusion: In the invasion front bcl-2 was expressed in 31 (45%), p53 in 37 (53%) and mdm-2 in 33 (47%) cases. HPV infection was detected in 40 (58%) cases. Carcinomas with a higher Ki-67 labeling index were more frequently HPV positive than HPV negative (82.5% vs 17.5%, p<0.01). No association was found between p53, mdm-2 or Ki-67 and either lymph node status or recurrence rate. Negative staining for bcl-2 was associated only with the presence of lymph node metastasis (74% vs 26%, p=0.05), and not with the recurrence rate. Significant correlation among expression of bcl-2, p53, mdm-2 oncoprotein and Ki-67 values was also observed. These results suggest that further study of a larger series is needed to confirm whether bcl-2, either alone or in combined evaluation with other markers, could be a useful marker to identify more aggressive behavior in early stage cervical carcinoma.