COX-2 and p53 in human sinonasal cancer: COX-2 expression is associated with adenocarcinoma histology and wood-dust exposure.
The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2 to development of cancer. Many signals that activate COX-2 also induce tumor suppressor p53, a transcription factor central in cellular stress response. We investigated COX-2 and p53 expressions by immunohistochemistry in 50 SNCs (23 adenocarcinomas, and 27 squamous cell carcinomas (SCC); 48 analyzed for COX-2; 41 for p53). Occupational histories and smoking habits were available for majority of the cases. Most of the adenocarcinoma cases with exposure history data had been exposed to wood dust at work in the past (88%, 14/16). For smokers, 63% (12/19) presented with SSC, whereas 64% (7/11) of nonsmokers displayed adenocarcinoma. COX-2 was expressed at higher levels in adenocarcinoma as compared to SSC (p < 0.001). COX-2 expression showed significant association with occupational exposure to wood dust (p = 0.024), and with nonsmoking status (p = 0.001). No statistically significant associations between the exposures and p53 accumulation were found; however, the p53 accumulation pattern (p = 0.062 for wood dust exposure) resembled that of COX-2 expression. In summary, our findings show increased COX-2 expression in SNC adenocarcinoma with wood dust exposure, suggesting a role for inflammatory components in the carcinogenesis process. In contrast, SCCs predominated among smokers and expressed COX-2 rarely; this may suggest at least partially different molecular mechanisms.
Holmila
Reetta
R
Finnish Institute of Occupational Health, Helsinki, Finland.
Cyr
Diane
D
Luce
Danièle
D
Heikkilä
Pirjo
P
Dictor
Michael
M
Steiniche
Torben
T
Stjernvall
Tuula
T
Bornholdt
Jette
J
Wallin
Håkan
H
Wolff
Henrik
H
Husgafvel-Pursiainen
Kirsti
K
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004391:Dust; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009669:Nose Neoplasms / Q000209:etiology / Q000378:metabolism*; D016273:Occupational Exposure / Q000009:adverse effects*; D010255:Paranasal Sinus Neoplasms / Q000209:etiology / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014934:Wood
D014408:Biomarkers, Tumor; D004391:Dust; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human