PURPOSE: Cyclooxygenase-2 (COX-2; PTGS2) is considered to play an important role in colorectal carcinogenesis and is often up-regulated in colon cancers. However, previous data on the influence of COX-2 expression on patient outcome have been conflicting. EXPERIMENTAL DESIGN: Using 662 colon cancers (stage I-IV) in two independent prospective cohorts (the Nurses' Health Study and the Health Professionals Follow-up Study), we detected COX-2 overexpression in 548 (83%) tumors by immunohistochemistry. Cox proportional hazards models were used to compute hazard ratios (HR) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and related molecular events, including the CpG island methylation phenotype, microsatellite instability, and p53, CIMP, KRAS, and BRAF mutations. RESULTS: During follow-up of the 662 cases, there were 283 deaths, including 163 colon cancer-specific deaths. Patients with COX-2-positive tumors showed a trend towards an inferior colon cancer-specific mortality [HR, 1.37; 95% confidence interval (95% CI), 0.87-2.14], which became significant after adjusting for tumor stage and other predictors of clinical outcome (multivariate HR, 1.70; 95% CI, 1.06-2.74; P = 0.029). Notably, the prognostic effect of COX-2 expression might differ according to p53 status (Pinteraction = 0.04). Compared with tumors with both COX-2 and p53 negative, COX-2-positive tumors were significantly associated with an increased cancer-specific mortality (multivariate HR, 2.12; 95% CI, 1.23-3.65) regardless of p53 status. A similar trend was observed when overall mortality was used as an outcome. CONCLUSION: COX-2 overexpression is associated with worse survival among colon cancer patients. The effect of COX-2 on clinical outcome may be modified by p53 status.
PURPOSE:Cyclooxygenase-2 (COX-2; PTGS2) is considered to play an important role in colorectal carcinogenesis and is often up-regulated in colon cancers. However, previous data on the influence of COX-2 expression on patient outcome have been conflicting. EXPERIMENTAL DESIGN: Using 662 colon cancers (stage I-IV) in two independent prospective cohorts (the Nurses' Health Study and the Health Professionals Follow-up Study), we detected COX-2 overexpression in 548 (83%) tumors by immunohistochemistry. Cox proportional hazards models were used to compute hazard ratios (HR) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and related molecular events, including the CpG island methylation phenotype, microsatellite instability, and p53, CIMP, KRAS, and BRAF mutations. RESULTS: During follow-up of the 662 cases, there were 283 deaths, including 163 colon cancer-specific deaths. Patients with COX-2-positive tumors showed a trend towards an inferior colon cancer-specific mortality [HR, 1.37; 95% confidence interval (95% CI), 0.87-2.14], which became significant after adjusting for tumor stage and other predictors of clinical outcome (multivariate HR, 1.70; 95% CI, 1.06-2.74; P = 0.029). Notably, the prognostic effect of COX-2 expression might differ according to p53 status (Pinteraction = 0.04). Compared with tumors with both COX-2 and p53 negative, COX-2-positive tumors were significantly associated with an increased cancer-specific mortality (multivariate HR, 2.12; 95% CI, 1.23-3.65) regardless of p53 status. A similar trend was observed when overall mortality was used as an outcome. CONCLUSION:COX-2 overexpression is associated with worse survival among colon cancerpatients. The effect of COX-2 on clinical outcome may be modified by p53 status.
Authors: C A Eads; K D Danenberg; K Kawakami; L B Saltz; C Blake; D Shibata; P V Danenberg; P W Laird Journal: Nucleic Acids Res Date: 2000-04-15 Impact factor: 16.971
Authors: F Cianchi; C Cortesini; P Bechi; O Fantappiè; L Messerini; A Vannacci; I Sardi; G Baroni; V Boddi; R Mazzanti; E Masini Journal: Gastroenterology Date: 2001-12 Impact factor: 22.682
Authors: Dingzhi Wang; Lingchen Fu; Wei Ning; Lixia Guo; Xiaofei Sun; Sudhansu K Dey; Rupesh Chaturvedi; Keith T Wilson; Raymond N DuBois Journal: Proc Natl Acad Sci U S A Date: 2014-04-24 Impact factor: 11.205
Authors: E L Wang; Z R Qian; M Nakasono; T Tanahashi; K Yoshimoto; Y Bando; E Kudo; M Shimada; T Sano Journal: Br J Cancer Date: 2010-02-09 Impact factor: 7.640