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


METHODS
Retrospective study.


METHODS
Patients with NPC were referred to the Department of Otolaryngology-Head and Neck Surgery for treatment.


METHODS
Formalin-fixed, paraffin-embedded NPC specimens from 42 patients were obtained.


METHODS
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.


METHODS
(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.
Soo
Ross
R
Department of Haematology-Oncology, National University Hospital, Singapore 119074, Singapore. soolk@nuh.com.sg
Putti
Thomas
T
Tao
Qian
Q
Goh
Boon-Cher
BC
Lee
Kang-Hoe
KH
Kwok-Seng
Loh
L
Tan
Luke
L
Hsieh
Wen-Son
WS
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000378:metabolism; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins; D019175:DNA Methylation; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; C484380:PDLIM7 protein, human; D042461:Vascular Endothelial Growth Factor A; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors