BAX AND BCL-2 EXPRESSIONS PREDICT RESPONSE TO RADIOTHERAPY IN HUMAN CERVICAL-CANCER

Purpose: The ratio of Bcl-2 to Bar expression determines survival or d eath following an apoptotic stimulus. In order to establish a new pred ictor of the outcome of treatment for human cervical carcinoma, we inv estigated the relationship between the expressions of the Bar and Bcl- 2 proteins and the response to radiotherapy after the administration o f 10.8 Gy. Methods: A total of 44 patients with histologically proven carcinoma of the uterine cervix, including three with recurrent cervic al stump carcinomas, were treated with definitive radiotherapy. The pr esence of mutations in exons 5-8 of the p53 gene was analyzed by a sin gle-strand conformation polymorphism analysis and DNA sequencing. Resu lts: Forty patients were found to have wild-type p53, and the remainin g four had mutant p53. The Bar and Bcl-2 protein expressions prior to radiotherapy did not correlate with response and survival. However, th e Bar and Bcl-2 protein expressions after radiotherapy correlated with both response and survival. Bar-positive tumors showed significantly better responses than the Bar-negative tumors after 10.8 Gy radiation (P = 0.0002). In contrast, the Bcl-2-positive tumors showed significan tly poorer responses than the Bcl-2-negative tumors after radiation (P = 0.002). Increased Bar expression after the 10.8 Gy radiotherapy was found to be correlated with good survival (P = 0.04). In contrast, in creased Bcl-2 expression after such radiotherapy was correlated with p oor survival (P = 0.002). Conclusion: The levels of Bar and Bcl-2 expr ession after 10.8 Gy radiotherapy are useful prognostic markers in pat ients with human cervical carcinoma.