bcl-2 immunoreactivity but not p53 accumulation associated with tumour response to radiotherapy in cervical carcinoma

Abstract

Purpose: This study seeks to define the role of pretreatment expression of the tumour-suppressor p53 protein and the anti-apoptotic protein bcl-2 and their relationship to tumour response to radiotherapy in cervical carcinoma. Methods: A total of 101 patients were evaluated and the possibility of a correlation done between the pretreatment status of the two proteins and clinical outcome following radiotherapy was investigated. Such patients were either disease-free (group 1, n=65) or had residual/recurrent disease (group 2, n=36) at a 16-month follow-up. p53 and bcl-2 protein expression was determined by immunocytochemistry. The presence of mutant p53 was detected by a mutant specific p53 enzyme-linked immunosorbent assay. Results: There was no correlation between p53 immunoreactivity or the presence of mutant p53 protein and disease status after treatment. Expression of bcl-2 protein, however, showed significant pretreatment correlations with the final disease outcome (r=0.643, P=0.0001). Moreover the odds ratio of a tumour expressing moderate to intense levels of bcl-2 responding poorly to radiotherapy was 27.2 (95% CI 6.0, 123.3). Conclusions: bcl-2 protein functions in an anti-oxidant pathway to prevent apoptosis. Since radiotherapy efficacy depends on adequate DNA damage caused by free-radical generation, increased expression of bcl-2 may result in tumours becoming less responsive to radiation. Mutation of the p53 gene, however, is a rare event in cervical cancer. Since bcl-2 is negatively regulated by p53, it could be presumed that the p53 detected in the tumour cells may be non-functional or inactive possibly because of interaction with proteins such as E6 or mdm-2.