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Overexpression of Cyclooxygenase-2 in Nasopharyngeal Carcinoma and Association With Epidermal Growth Factor Receptor Expression
Ross Soo, MD;
Thomas Putti, MD;
Qian Tao, PhD;
Boon-Cher Goh, MD;
Kang-Hoe Lee, MD;
Loh Kwok-Seng, MD;
Luke Tan, MD;
Wen-Son Hsieh, MD
Arch Otolaryngol Head Neck Surg. 2005;131:147-152.
Objectives To examine the association between cyclooxygenase-2 (COX-2) expression with epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), and latent membrane protein 1 (LMP-1) expression and with COX-2 promoter methylation status in primary nasopharyngeal cancer (NPC) tumors and to determine COX-2 promoter methylation status in NPC cell lines.
Design Retrospective study.
Setting Patients with NPC were referred to the Department of Otolaryngology–Head and Neck Surgery for treatment.
Patients Formalin-fixed, paraffin-embedded NPC specimens from 42 patients were obtained.
Interventions Immunohistochemical expression of COX-2, EGFR, VEGF, iNOS, and LMP-1 was performed in 42 NPC samples. COX-2 promoter methylation status was studied in 20 separate specimens and in 4 NPC cell lines.
Main Outcome Measures (1) COX-2, EGFR, VEGF, iNOS, and LMP-1 expression; and (2) COX-2 promotor methylation status.
Results COX-2 was overexpressed in 79% of NPC specimens and was associated with EGFR status (P = .03) but not with LMP-1 or iNOS. In primary NPC tissue, methylation of the COX-2 promoter was seen in 4 of 7 COX-2–negative and 1 of 13 COX-2–positive immunohistochemical cases. COX-2 promoter methylation was found in the CNE-1 cell line.
Conclusions Nasopharyngeal cancer may be a useful target for selective COX-2 inhibition. The absence of promoter methylation may be a necessary component of COX-2 overexpression, and promoter methylation may be one of the mechanisms that regulate COX-2 expression.
Author Affiliations: Departments of Haematology-Oncology (Drs Soo and Goh), Pathology (Dr Putti), Medicine (Dr Lee), and Otolaryngology–Head and Neck Surgery (Drs Kwok-Seng and Tan), National University Hospital, and Cancer Epigenetics/Tumor Virology Laboratory, Division of Biomedical Sciences, Johns Hopkins in Singapore (Drs Tao and Hsieh), Singapore.
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JCO 2005;23:6730-6738.
ABSTRACT
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