Apoptotic and proliferative indexes in esophageal cancer: Predictors of response to neoadjuvant therapy apoptosis and proliferation in esophageal cancer

Altered expression of the genes that control apoptosis and proliferation may influence the response of cancer cells to cytotoxic agents. The primary aim of this study was to determine the role of the novel an-tiapoptotic and cell cycle gene, survivin, in apoptotsis and proliferation in esophageal cancer and to evaluate whether the survivin, p53, and bcl-2 status were able to predict a patient’s response to neoadjuvant therapy. A total of 104 patients with esophageal tumors were studied. Tumor tissue was immunostained for survivin, p53, and bcl-2 proteins. Proliferative and apoptotic activity was measured using ki-67 immu-nohistochemical analysis and the TUNEL method, respectively. Forty-eight patients whose pretreat-ment biopsies were analyzed received neoadjuvant chemoradiation therapy or chemotherapy followed by surgery. Outcome was graded as a complete response, a partial response, or no response according to the results of histologic examination and CT imaging. Expression of survivin was found to correlate significantly with the proliferative index but not the apoptotic index. Patients who received neoadjuvant treatment were more likely to achieve a complete response if their tumors had high proliferative activity, and p53 positive tumors were more likely to contain residual tumor after treatment. In conclusion, survivin expression appears to foster proliferative activity in esophageal cancer, and tumors with a high proliferative index or a functioning p53 gene are more responsive to neoadjuvant chemoradiation therapy. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation). Supported by grants from the Royal College of Surgeons of England and Yorkshire Cancer Research.