Apoptotic and proliferative indexes in esophageal cancer: predictors of response to neoadjuvant therapy [corrected].
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 antiapoptotic 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 immunohistochemical analysis and the TUNEL method, respectively. Forty-eight patients whose pretreatment 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.
Beardsmore
Duncan M
DM
Academic Department of Surgery, St James's University Hospital, Leeds, United Kingdom. meddmb@stjames.leeds.ac.uk
Verbeke
Caroline S
CS
Davies
Claire L
CL
Guillou
Pierre J
PJ
Clark
Geoffrey W B
GW
D000230:Adenocarcinoma / Q000737:chemistry / Q000503:physiopathology / Q000628:therapy; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000503:physiopathology / Q000628:therapy; D002455:Cell Division; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53