Development of Clinically Applicable Molecular Markers Distinguishing Sinonasal Undifferentiated Carcinoma from Sinonasal Squamous Cell Carcinoma

Background: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. Moreover, reliable histopathologic markers that distinguish SNUC from poorly differentiated sinonasal squamous cell carcinoma (SNSCC) are lacking. Distinguishing between SNSCC and SNUC has significant clinical importance since the prognosis and treatment strategies are different. Therefore, new diagnostic molecular markers for SNUC are needed. Previously, we have reported gene expression levels of seven markers completely distinguished SNUCs from SNSCCs. However, the use of those single transcripts as biomarkers has many limitations, since measurement of absolute transcript expression is methodology dependent and relies on normalization through housekeeping genes. To enhance the potential clinical relevance of our finding, we introduced the top scoring pairs algorithm to identify molecular markers that distinguish the two tumor types regardless of the gene expression assay platform.

Methods: Formalin-fixed paraffin-embedded tumor specimens obtained from 15 treatment-naïve SNUC and 6 treatment-naïve SNSCC were used in this study. Gene expression analysis of the specimens was performed using an HTG oncology biomarker panel. To identify pairs of genes that distinguish SNUCs from SNSCCs, the top-scoring-pair analysis was employed on 132 differentially expressed genes between SNUCs and SNSCCs.

Results: We identified 104 gene pairs that separated SNUCs from SNSCC perfectly (area under the curve = 1.00). Among these pairs, the following gene pairs can be used as potential diagnostic markers to distinguish SNUCs from SNSCCs because of their great difference of gene expression levels between two genes and easy availability of their detection probes in the market; the gene pairs whose expression of the first gene is lower than the second gene in SNUC are KRT16CLCA2, STMN1 > NDRG1 and FANCL > ITGB6.

Conclusion: We successfully identified new diagnostic pairs of markers that distinguish SNUCs from SNSCCs. Since these gene pairs can be measured regardless of the gene expression assay platform, they might serve as clinically applicable diagnostic markers.