PROLIFERATION AND APOPTOSIS BEFORE AND AFTER RADIOCHEMOTHERAPY IN RECTAL-CANCER

Purpose: To investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p 53 in rectal cancer before and after radiochemotherapy. Materials and Methods: Thirty-two patients dispositioned to receive preoperative rad iochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biops ies and the final resected specimens after radiochemotherapy were avai lable for analyses. Apoptotic cells were identified and quantified usi ng in situ end labeling (ISEL) technique. The proliferative activity w as determined by immunohistochemical assessment of the Ki67 (MIB-1) an tigen. p53 expression was analysed immunohistochemically as well. A cl inical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected a fter radiochemotherapy. Results: After radiochemotherapy, the apoptoti c index increased significantly in almost every case examined. In cont rast, the proliferative activity was significantly decreased when comp aring biopsies and resected specimens. Tumors that were immunohistoche mically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find ally correlation be tween the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging. Conclusion: Our results indica te, that radiochemotherapy induces an increase in apoptotic cell death . The observation of higher rates of apoptosis in p53 negative tumors suggests that p53 might be a regulator of apoptosis in rectal cancer.