Bcl-2-/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with rectal cancer

Combined radiation therapy and chemotherapy are adjuvant treatments given a fter surgery to patients with rectal carcinoma. Because apoptosis seems to play a role in tumor response to radiotherapy, the current study investigat es whether there is a correlation between the ratio of bcl-2 oncoprotein an d bax expression in rectal adenocarcinoma and the clinical response to radi otherapy. Elective colectomy for primary rectal adenocarcinoma followed by adjuvant radiotherapy and chemotherapy was performed on 35 patients. Tumors were staged as B-2 (n = 30) and C (n = 5), and were classified as radiatio n resistant (n = 19, group A) and radiation nonresistant (n = 16, group B). Immunohistochemical study, using the streptavidin-biotin complex technique and monoclonal antibody to bcl-2 and polyclonal antibody to bax. protein w as used on paraffin sections. Cases were considered positive if at least 5% of tumor cells displayed cytoplasmic staining for bcl-2 or bax. In each tu mor, the bcl-2/bax ratio was calculated dividing the percentage of bcl-2-po sitive cells by the percentage of bax-positive cells. For statistical analy sis, the Mann-Whitney rank sum test and Kruskal-Wallis analysis of variance test were used. Rectal tumors of group A displayed significantly greater b cl-2 immunoreactivity (40.2 +/- 4.2) compared with group B (20.2 +/- 3.8). In contrast, expression of bax protein was less in group A (30.3 +/- 3.3) c ompared with group B (41.3 +/- 2.3). The bel-2/bax ratio was greater in gro up A (1.3 +/- 0.1) compared with group B (0.49 +/- 0.1), and was correlated with poor responsiveness to radiotherapy. The current study indicates that in patients with rectal carcinoma an elevated bcl-2/bax ratio in tissue sp ecimens suggests increased tumor resistance to adjuvant radiotherapy. Thus, in such patients, the bcl-2/bax ratio may serve as a potential molecular m arker for prediction of tumor prognosis.