Genetic profiling of poorly differentiated sinonasal tumours

Abstract

The sinonasal cavities harbour a variety of rare tumour types. Many carry a poor prognosis while therapeutic options are limited. Histopathological classification can be difficult, especially for poorly differentiated tumours such as olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC). We analysed Affymetrix OncoScan genome-wide copy number profiles of these three tumour types, both as originally diagnosed and as regrouped by their cytokeratin (Ck) and neuroendocrine (Ne) expression pattern, aiming to find a relation between phenotype and genotype. According to the original histopathological classification our series consisted of 24 ONB, 11 SNEC and 19 SNUC, while immunohistochemistry indicated 11 Ck−Ne+/ONB, 18 Ck+Ne+/SNEC, 24 Ck+Ne−/SNUC, and 1 Ck−Ne−/unclassified. As originally diagnosed, the three tumour types showed similar copy number profiles. However, when regrouped by Ck/Ne immunostaining we found a distinct set of gains and losses; Ck−Ne+/ONB harboured few and predominantly whole chromosomes abnormalities, Ck+Ne+/SNEC carried both gains and losses in high frequency, and Ck+Ne−/SNUC showed mostly gains. In addition, each tumour carried a number of unique chromosomal deletions. Genome-wide copy number profiling supports the value of immunohistochemical CkNe staining of ONB, SNEC and SNUC for tumour classification, which is important for prognosis and therapeutic decision-making.