Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
To evaluate seven molecular markers including cyclooxygenase -2, epidermal growth factor receptor, Ki-67, p21, survivin, thymidylate synthase, and vascular endothelial growth factor for prediction of response to preoperative chemoradiotherapy in locally advanced rectal cancer. Fifty-four patients with clinical T3-4 and/or node-positive rectal cancer who underwent preoperative chemoradiotherapy followed by surgical resection were enrolled into this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic irradiation with concomitant 5-fluorouracil or oral capecitabine. Expression of molecular markers in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemical staining on the tissue microarray. Tumor downstaging was used as an endpoint for evaluation of tumor response. Tumor downstaging was observed in 22 patients (41%), and pathologic complete remission in 7 patients (13%). Among seven molecular markers, only survivin expression was significantly related with tumor downstaging: 26% with high survivin expression (>75% in extent) vs. 72% with low survivin expression (p = 0.0011). However, other six molecular markers were found not to have any correlation with tumor downstaging. High survivin expression in pretreatment tumor biopsy was associated with less tumor downstaging after preoperative chemoradiotherapy for locally advanced rectal cancer.