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Prognostic Significance of Cyclooxygenase-2 Overexpression in Glottic Cancer

Authors' Affiliations: ¹ Pathology Department, ² Cancer Research Center, and ³ Radiation Oncology Department, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Quebec, Canada; ⁴ Radiation Oncology Department, Hôpital Notre-Dame, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; ⁵ Hôpital Fleurimont, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada; and ⁶ Complexe Hospitalier de la Sagamie, Chicoutimi, Quebec, Canada

Requests for reprints: Bernard Têtu, Department of Pathology, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, 11, Cote Du Palais, Quebec, Quebec, Canada G1R 2J6. Phone: 418-691-5233; Fax: 418-691-5226; E-mail: bernard.tetu{at}chuq.qc.ca.

Purpose: Cyclooxygenase-2 (COX-2) overexpression has been associated with a poor prognosis in many cancers. However, the role of COX-2 overexpression in head and neck cancers remains undetermined. The objective of this study was to evaluate whether COX-2 is a prognostic factor in glottic cancer.

Experimental Design: This study was part of a phase III placebo-controlled randomized trial evaluating the efficacy of -tocopherol in reducing second primary cancers (SPC) in head and neck cancer patients. Immunohistochemical analyses were conducted on pretreatment biopsies of 301 patients with early-stage glottic cancer treated by radiotherapy. The median value of 50% of positive tumor cells was the cutoff point used to define COX-2 overexpression. Outcomes considered in the statistical analysis were recurrence, SPC, and death. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and their 95% confidence intervals (95% CI).

Results: The HR associated with COX-2 overexpression was 0.94 (95% CI, 0.55-1.62) for recurrence. The HR associated with SPC was 2.63 (95% CI, 1.32-5.23) for the first 3.5 years of follow-up and 0.55 (95% CI, 0.22-1.32) for the following 3.5 years. The HR associated with COX-2 overexpression was 1.57 (95% CI, 1.01-2.45) for overall mortality.

Conclusions: COX-2 overexpression in glottic cancer was associated with increased overall mortality and an increased risk of SPC during the early follow-up period. Future studies are needed to explain observed effects on SPC. COX-2 expression may prove helpful in defining an individual patient's prognosis.