Expression of hypoxia-inducible factor 1α predicts clinical outcome after preoperative hyperthermo-chemoradio therapy for locally advanced rectal cancer

Hypoxia-inducible factor 1α (hif-1α) is an intrinsic marker of tumor hypoxia. it has been considered that hypoxic conditions reduce radiosensitivity,but the role of hif-1α in patients treated with preoperative therapy for rectal cancer is still unclear. the aim of this study was to evaluate the predictive value of tumor response to preoperative hyperthermo-chemoradiotherapy (hcrt) and the prognostic significance of hif-1α expression in patients with locally advanced rectal cancer. between 2003 and 2006,50 patients with histologically proven rectal adenocarcinoma who underwent hcrt followed by surgery were investigated. hif-1α expression was immunohistochemically evaluated using pre-treatment biopsies. the total radiation dose was 40-50 gy and chemotherapy consisted of 5-fu and lv administered by continuous infusion on day 1-5,day 15-19,and day 29-33 during radiotherapy. hyperthermia treatment was performed for once a week for 2-5 sessions. the surgical operation was performed 8 weeks after hcrt and each resected specimen was graded by histological criteria of the japanese classification of colorectal carcinoma. the effects of hif-1α on clinical outcomes were analyzed by univariate and multivariate analysis. positive hif-1α expression was recognized in 42. 0% of samples (21/50). resected specimens that showed pathological grades 1,2,and 3 numbered 17,24,and 9 cases,respectively. there were no significant differences between the hif-1α-positive group and hif-1α-negative group for pathological grading and pcr. overall survival (os) rate at 3 years in the hif-1α-negative group was 85. 2%,which was significantly better than the 60. 6% in the hif-1α-positive group. recurrence-free survival (rfs) rate at 3 years in the hif-1α-negative group was 82. 8%,being significantly better than 47. 6% in the hif-1α-positive group. in addition,elevated hif-1α expression was significantly correlated with recurrence-free survival and metastasis-free survival rate in multivariate analysis. hif-1α expression might be predictive of recurrence-free survival and metastasis-free survival rate for rectal cancer patients treated with hcrt.