Cyclooxygenase 2 expression in rectal cancer is of prognostic significance in patients receiving preoperative radiotherapy.
SourceClinical Cancer Research, 13, 10, (2007), pp. 2955-2960
Article / Letter to editor
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Clinical Cancer Research
SubjectNCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 2: Age-related aspects of cancer; ONCOL 3: Translational research; UMCN 1.2: Molecular diagnosis, prognosis and monitoring
PURPOSE: To determine the effect of cyclooxygenase (COX)-2 expression on clinical behavior in irradiated and nonirradiated rectal carcinomas. EXPERIMENTAL DESIGN: Tumor samples were collected from 1,231 patients of the Dutch TME trial, in which rectal cancer patients were treated with standardized surgery and randomized for preoperative short-term (5 x 5 Gy) radiotherapy or no preoperative radiotherapy. Tissue microarrays were constructed from primary tumor material, and COX-2 expression was assessed by immunohistochemistry. Tumor cell apoptosis was determined by M30 immunostaining. RESULTS: A high level of COX-2 expression after radiotherapy was associated with low levels of tumor cell apoptosis (P=0.001). COX-2 expression had no significant effect on patient survival or tumor recurrence in nonirradiated tumors. However, in patients receiving preoperative radiotherapy, high level of COX-2 expression was associated with higher incidence of distant recurrences [P=0.003; hazard ratio (HR), 1.7; 95% confidence interval (95% CI), 1.2-2.5] and shorter disease-free survival (P=0.002; HR, 1.8; 95% CI, 1.2-2.5) and overall survival (P=0.009; HR, 1.5; 95% CI, 1.1-2.0), independent of patient age, tumor stage, tumor location, or the presence of tumor cells in the circumferential resection margin. CONCLUSIONS: A high level of COX-2 expression after preoperative radiotherapy in resection specimens is associated with apoptosis resistance, high distant recurrence rates, and a poor prognosis in rectal cancer.
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