GENOME-WIDE ANALYSIS OF GENETIC CHANGES IN INTESTINAL-TYPE SINONASAL ADENOCARCINOMA

Abstract: Background. Intestinal-type sinonasal adenocarcinomas are rare tumors related to professional exposure to wood dust. Little is known about the genetic changes in these tumors. Methods. Twenty-two tumors were analyzed by microarray comparative genomic hybridization (CGH). In addition, DNA ploidy was measured by flow cytometry and microsatellite instability (MSI) by multiplex PCR. Results. The most frequent gains were, in descending order, as follows: 5p15, 20q13, and 8q24. Losses occurred most frequently at 4q31-qter, 18q12-22, 8p12-pter, and 5q11-qter. MSI was not detected. Seven cases that harbored very few changes were mostly DNA diploid and had more favorable clinicopathological features, such as lack of intracranial invasion, less metastases, and longer overall survival. Conclusion. The microarray CGH results enabled to better define hotspots of chromosomal gains and losses for further investigation of genes involved in the tumorigenesis of sinonasal adenocarcinoma. In addition, the data allowed classification of a group of patients with better clinical outcome. Intestinal-type sinonasal adenocarcinomas (ITACs) are epithelial tumors of the nasal cavities and paranasal sinuses, often related to professional exposure to wood dust. It is a rare neoplasm, representing 8% to 25% of all malignant sinonasal cancer. The incidence is less than 1 case per 100,000 inhabitants per year, 1-3 occurring predominately among men with a mean age of presentation of 60 to 65 years. 3 It is located most frequently (85%) in the ethmoid sinus and the upper part of the nasal cavity. It only exceptionally arises in the other sites of the nasal cavity (maxillary sinus in 10%), and these cases are usually not related to wood dust exposure. Local recurrence (30% to 60%) and invasion of the duramater constitute the main causes of death among patients, 4 whereas distant and lymph node metastasis are exceptional (5% to 10%). Standard therapeutic modalities include surgery followed by radiotherapy in advanced stages, sometimes with chemotherapy treatment. Five pathological types of sinonasal ITAC are distinguished as follows: papillary, colonic, solid, mucinous (alveolar goblet and signet ring), an