Introduction. Despite their histological resemblance to colorectal adenocarcinoma, there is some information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). To evaluate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) gene defects in ITAC, by investigating the immunohistochemical expression of TRAIL gene product in a group of ethmoidal ITACs associated with occupational exposure. Material and Methods. Retrospective study on 23 patients with pathological diagnosis of primary ethmoidal ITAC. Representative formalin-fixed, paraffin-embedded block from each case was selected for immunohistochemical studies using the antibody against TRAIL. Clinicopathological data were also correlated with the staining results. Results. The immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of TRAIL expressing cells compared to well-differentiated cases. No correlation was found with other clinicopathological parameters, including T, stage and relapses. Conclusion. The relationship between upregulation of TRAIL and poorly differentiated ethmoidal adenocarcinomas suggests that the mutation of this gene, in combination with additional genetic events, could play a role in the pathogenesis of ITAC. 1. Introduction Malignant tumors of the nasal cavity and paranasal sinuses account for 0.2% of all human primary malignant neoplasms, with an incidence of 0.1–1.4 new cases/year/100,000 inhabitants [1–3]. Adenocarcinomas account for 10–20% of all primary malignant neoplasms of the sinonasal tract [4, 5]. Many of these have salivary gland origin, while others have histologic patterns resembling those of colon adenocarcinoma. This second type of sinonasal adenocarcinoma has been named intestinal-type adenocarcinoma (ITAC) and is responsible for less than 4% of the total malignancies of this region [6]. ITACs of the nasal cavity and paranasal sinuses can occur sporadically or are associated with occupational exposure to hardwood and leather dusts [7]. Exposure to wood and leather dusts increases the risk of adenocarcinoma by 500-fold [8, 9]. Findings from several studies have suggested clinical differences between ITAC arising in individuals with occupational dust exposure and ITAC arising sporadically. In fact tumors related to occupational exposure affect men in 85–90% of cases, showing a strong tendency to arise in the ethmoid sinuses [10–12]. ITACs are aggressive tumors characterized by frequent local recurrences, low incidence of distant metastases,
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