Cyclooxygenase-2 expression in pretreatment biopsy as a predictor of tumor responses after preoperative chemoradiation in rectal cancer

Objective: To determine whether cyclooxygenase-2 (COX-2) expression in pretreatment biopsy specimens is a useful predictive marker of tumor response to preoperative chemoradiation (CRT) in rectal cancer. Design: Case series. Setting: Colorectal cancer clinic. Patients: Thirty patients with locally advanced rectal cancer were given preoperative CRT of 5040 cGy for 6 weeks with concurrent administration of 5-fluorouracil and leucovorin. Main Outcome Measures: Immunohistochemical staining for COX-2 and angiogenesis markers (vascular endothelial growth factor, thymidine phosphorylase, and CD34) were performed on biopsy specimens obtained before preoperative CRT. The responses to preoperative CRT were assessed by radiologic downsizing (measured using magnetic resonance imaging volumetry), histopathologic downstaging, and a 3-point tumor regression grade (TRG) evaluation, based on the ratio of residual cancer to fibrosis. Results: Tumor downstaging was seen in 15 patients (50.0%) and nodal downstaging was noted in 14 patients (46.7%). Tumor regression grade 1 (good response) was shown by 7 patients (23.3%); TRG2 (moderate response) in 15 patients (50.0%); and TRG3 (poor response) in 8 patients (26.7%). Patients with COX-2 overexpression were more likely to show a poor TRG (P=.003) and were less likely to achieve histopathologic nodal downstaging (P=.03) than those with normal COX-2 expression. Vascular endothelial growth factor overexpression was found to be associated with COX-2 overexpression (P=.02). Conclusions: Overexpression of COX-2 in pretreatment biopsies might be predictive of poor tumor regression after preoperative CRT. Administration of COX-2 inhibitors to patients with COX-2 overexpression, in an attempt to improve response rate to preoperative CRT, warrants assessment in clinical trials.