Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with epidermal growth factor receptor expression

Arch Otolaryngol Head Neck Surg. 2005 Feb;131(2):147-52. doi: 10.1001/archotol.131.2.147.

Abstract

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Carrier Proteins / metabolism
  • Cyclooxygenase 2
  • Cytoskeletal Proteins
  • DNA Methylation
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Male
  • Membrane Proteins
  • Middle Aged
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Membrane Proteins
  • PDLIM7 protein, human
  • Vascular Endothelial Growth Factor A
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • ErbB Receptors