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.

An update on head and neck cancer: new entities and their histopathology, molecular background, treatment, and outcome

“…A similar overlap in copy number alterations between neuroendocrine carcinoma of the salivary gland a lung has also been reported . Similarly, only few data on the mutational landscape of olfactory neuroblastoma are available with preferential affection of TP53 and a heterogeneous pattern of copy‐number alterations .…”

“…Data on the molecular features of olfactory neuroblastoma and sinonasal neuroendocrine carcinoma (SNEC) are limited. In small cell SNEC, the pattern of copy-number alterations is complex and genetics seem to show overlap with small cell neuroendocrine carcinoma of the lung with mutations of TP53 and RB1, upregulation of BCL2 signaling, and activation of MYC and PI3K pathways (86,92). A similar overlap in copy number alterations between neuroendocrine carcinoma of the salivary gland a lung has also been reported (93).…”

Sinonasal cancer: an overview of the emerging subtypes

“…The use of molecular biology techniques is, at the present time, of great help to characterise these tumours in a more precise way. 32,33 Indeed, pathology appears to be the most important predictor of five-year survival. 34 These new diagnostic entities are well-defined in terms of their underlying aetiology, which holds promise for the development of novel therapeutic targets.…”

Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside

“…Few comprehensive molecular studies have been conducted to date, the majority of which look at multiple tumour types. Lopez and co-workers' classification of subtype based on specific marker expression and copy number alterations demonstrated that SNECs typically stain positive for both cytokeratin and neuroendocrine markers, in contrast to SNUCs and ONBs and exhibit many copy number alterations with a high level of chromosomal instability [54]. In another study assessing the status of MiR-21 as a potential prognostic marker, the authors found that the marker was upregulated in their tumour cohort, which consisted of a small minority of SNECs [55].…”