Proliferation und Apoptose vor und nach praoperativer simultaner Radiochemotherapie von Rektumkarzinomen

Purpose: To investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p53 in rectal cancer before and after radiochemotherapy. Materials and Methods: Thirty-two patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biopsies and the final resected specimens after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected after radiochemotherapy. Results: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased when comparing biopsies and resected specimens. Tumors that were immunohistochemically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging. Conclusion: Our results indicate, 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.