TY - JOUR
T1 - Tumor COX-2 expression and prognosis of patients with resectable pancreatic cancer
AU - Matsubayashi, Hiroyuki
AU - Infante, Jeffrey R.
AU - Winter, Jordan
AU - Klein, Alison P.
AU - Schulick, Richard
AU - Hruban, Ralph
AU - Visvanathan, Kala
AU - Goggins, Michael
N1 - Funding Information:
This work was supported by the NCI grant (CA90709, CA62924) and the Michael Rolfe Foundation.
PY - 2007/10
Y1 - 2007/10
N2 - Background: COX-2 is overexpressed in many cancers and precursor neoplasms including pancreatic cancer and in experimental settings its overexpression has multiple tumorigenic effects including increasing proliferation and angiogenesis, and inhibition of apoptotic and immunologic responses. We evaluated the prognostic significance of COX-2 expression in pancreatic adenocarcinomas. Patients and Methods: We analyzed COX-2 expression by immunohistochemistry in a prospective cohort of 299 patients with resectable infiltrating adenocarcinoma of the pancreas that had undergone a pancreaticoduodenectomy at Johns Hopkins Hospital between January of 1998 and July of 2003. The survival associated with COX-2 expression was assessed by Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models that controlled for other known prognostic factors associated with pancreas cancer mortality. Results: By Kaplan-Meier analysis, patients whose pancreatic cancer cells expressed COX-2 (median survival, 15 months) had a significantly worse prognosis than patients whose tumor cells did not express COX-2 (median survival, 20 months; log rank, p = 0.002). In the multivariate Cox regression model (which included tumor size, node status, margin status, histologic grade and age), COX-2 expression remained independently prognostic of a worse survival with a hazard ratio (HR) of 1.41 (95% CI 1.08-1.84, p = 0.01). However, the adverse prognosis associated with COX-2 expression appeared greater in larger tumors: For tumors ≥3 cm in diameter, the HR was HR of 1.52 (95% CI 1.04-2.22) versus 1.11 (95% CI 0.75-1.67) in cancers <3 cm. Conclusions: Tumor COX-2 expression portends a poor prognosis for patients with resected adenocarcinoma of the pancreas, particularly in tumors ≥3 cm.
AB - Background: COX-2 is overexpressed in many cancers and precursor neoplasms including pancreatic cancer and in experimental settings its overexpression has multiple tumorigenic effects including increasing proliferation and angiogenesis, and inhibition of apoptotic and immunologic responses. We evaluated the prognostic significance of COX-2 expression in pancreatic adenocarcinomas. Patients and Methods: We analyzed COX-2 expression by immunohistochemistry in a prospective cohort of 299 patients with resectable infiltrating adenocarcinoma of the pancreas that had undergone a pancreaticoduodenectomy at Johns Hopkins Hospital between January of 1998 and July of 2003. The survival associated with COX-2 expression was assessed by Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models that controlled for other known prognostic factors associated with pancreas cancer mortality. Results: By Kaplan-Meier analysis, patients whose pancreatic cancer cells expressed COX-2 (median survival, 15 months) had a significantly worse prognosis than patients whose tumor cells did not express COX-2 (median survival, 20 months; log rank, p = 0.002). In the multivariate Cox regression model (which included tumor size, node status, margin status, histologic grade and age), COX-2 expression remained independently prognostic of a worse survival with a hazard ratio (HR) of 1.41 (95% CI 1.08-1.84, p = 0.01). However, the adverse prognosis associated with COX-2 expression appeared greater in larger tumors: For tumors ≥3 cm in diameter, the HR was HR of 1.52 (95% CI 1.04-2.22) versus 1.11 (95% CI 0.75-1.67) in cancers <3 cm. Conclusions: Tumor COX-2 expression portends a poor prognosis for patients with resected adenocarcinoma of the pancreas, particularly in tumors ≥3 cm.
KW - Cox-2
KW - Expression
KW - Immunohistochemistry
KW - Pancreatic cancer
KW - Pancreaticoduodenectomy
KW - Prognosis
KW - SPARC
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U2 - 10.4161/cbt.6.10.4711
DO - 10.4161/cbt.6.10.4711
M3 - Article
C2 - 18000398
AN - SCOPUS:41649094069
SN - 1538-4047
VL - 6
SP - 1569
EP - 1575
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 10
ER -