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.

Figure 1. Representative examples of COX-2 expression in sinonasal cancer

A) strong expression of COX-2 (+++) in ethmoidal adenocarcinoma; B) moderate expression of COX-2 (++) in SCC from nasal septum; C) no expression of COX-2 (−) in ethmoidal adenocarcinoma; D) no expression in SCC from nasal cavity. The original magnification was 100× in each example (A–D).

Figure 2. Distribution of COX-2 expression according to tumour histology in sinonasal cancer

(−/+): weak or no expression of COX-2; (++/+++): moderate or strong expression of COX-2.

Figure 3. Distribution of COX-2 expression in sinonasal carcinomas by exposure and tumour histology

(−/+): weak or no expression of COX-2; (++/+++): moderate or strong expression of COX-2.

Figure 4. Comparison between COX-2 mRNA expression (real time quantitative PCR assay) and COX-2 immunohistochemisty (IHC) in sinonasal adenocarcinoma

Real time quantitative PCR results are expressed as relative units, and IHC results as COX-2 index (percentage of COX-2 positive cells x intensity of COX-2 staining). The +/− sign in parentheses under the tumour codes mark the IHC classification as in Figures 3 and 4.