COX‐2 and p53 in human sinonasal cancer: COX‐2 expression is associated with adenocarcinoma histology and wood‐dust exposure

Abstract

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. © 2008 Wiley‐Liss, Inc.

Benign Lesions in Mucosa Adjacent to Intestinal-Type Sinonasal Adenocarcinoma

“…In addition, we confirmed a tendency of higher p53 positivity in the samples from patients with wood etiology, but not in the number of samples with some p53 positivity. Studying both ITAC and sinonasal squamous carcinoma, Holmila and coworkers also noted a trend for higher p53 expression in wood dust-related patients [19]. We found no difference in p53 expression between smokers and nonsmokers, and this was also seen by Holmila et al [19].…”

Mutations in TP53 tumor suppressor gene in wood dust‐related sinonasal cancer

“…2,52 In our recent study on a subset of the current sinonasal cancers, cyclooxygenase-2 protein, an enzyme associated with inflammation and DNA damage, and known to interact with p53, was shown to be highly expressed in adenocarcinomas in association to wood-dust exposure. 53 In summary, our current molecular epidemiology study demonstrates a high load of TP53 mutations in human sinonasal cancer, with the occurrence of TP53 mutation significantly increased in association to long duration and high level of exposure to wood dust. Smoking was not observed to influence the overall risk of having a TP53 mutation, but was associated with multiple TP53 mutations.…”

Genomic profiling of sinonasal squamous cell carcinoma

“…13,14 Until the present moment, genetic studies on sinonasal SCCs have demonstrated TP53 mutations and p53 overexpression in up to 56% of cases. [15][16][17] Kras mutations have been reported, but only in 1% of cases. 18 Bandoh et al 16 suggested that TP53 mutations and a low apoptotic index are associated with poor survival.…”

“…Cyclooxygenase 2 (COX2) expression was observed in low frequency, which may rule out a possible role for chronic inflammation in sinonasal SCC development. 17 Using loss of heterozygosity analysis, Götte et al 19 have shown losses on chromosomes 3p, 8p, 17p, and 18q. There are very few genome-wide studies on genetic changes in sinonasal SCC.…”