Sex determining region Y-box 2 (SOX2) amplification is an independent indicator of disease recurrence in sinonasal cancer.

The transcription factor SOX2 (3q26.3-q27) is an embryonic stem
cell factor contributing to the induction of pluripotency in
terminally differentiated somatic cells. Recently, amplification of
the SOX2 gene locus has been described in squamous cell carcinoma
(SCC) of different organ sites. Aim of this study was to
investigate amplification and expression status of SOX2 in
sinonasal carcinomas and to correlate the results with
clinico-pathological data. A total of 119 primary tumor samples
from the sinonasal region were assessed by fluorescence in-situ
hybridization and immunohistochemistry for SOX2 gene amplification
and protein expression, respectively. Of these, 59 were SSCs, 18
sinonasal undifferentiated carcinomas (SNUC), 10 carcinomas
associated with an inverted papilloma (INVC), 19 adenocarcinomas
(AD) and 13 adenoid cystic carcinomas (ACC). SOX2 amplifications
were found in subsets of SCCs (37.5%), SNUCs (35.3%), INVCs (37.5%)
and ADs (8.3%) but not in ACCs. SOX2 amplification resulted in
increased protein expression. Patients with SOX2-amplified
sinonasal carcinomas showed a significantly higher rate of tumor
recurrences than SOX2 non-amplified tumors. This is the first study
assessing SOX2 amplification and expression in a large cohort of
sinonasal carcinomas. As opposed to AD and ACC, SOX2 amplifications
were detected in more than 1/3 of all SCCs, SNUCs and INVCs. We
therefore suggest that SNUCs are molecularly closely related to
SCCs and INVCs and that these entities represent a subgroup of
sinonasal carcinomas relying on SOX2 acquisition during
oncogenesis. SOX2 amplification appears to identify sinonasal
carcinomas that are more likely to relapse after primary therapy,
suggesting that these patients might benefit from a more aggressive
therapy regime.