Sox2 and βIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas

Abstract

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed βIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger βIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and βIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.

Top IHC/ISH Hacks for and Molecular Surrogates of Poorly Differentiated Sinonasal Small Round Cell Tumors

“…Sox2 expression is normally restricted to stem cells; its aberrant overexpression has been linked to the ability to promote tumorigenicity and a poorly differentiated morphology [ 18 – 20 ]. Sox2 expression and gene amplification have been identified as common events in the head and neck [ 21 , 22 ]; in the sinonasal region, amplification and/or overexpression of Sox2 has been demonstrated in squamous carcinoma (SNSCC), sinonasal undifferentiated carcinoma (SNUC), adenoid cystic carcinoma (AdCC), and intestinal type adenocarcinoma (ITAC) [ 22 – 24 ]. Although the literature is controversial regarding SOX2 amplification/Sox2 expression, recent data highlight the driver role of SOX2 in stemness with Sox2 overexpression and poor outcomes in patients with solid tumors [25] .…”

“…Although the literature is controversial regarding SOX2 amplification/Sox2 expression, recent data highlight the driver role of SOX2 in stemness with Sox2 overexpression and poor outcomes in patients with solid tumors [25] . Sox2 expression is also associated with resistance to chemotherapy through a plethora of mechanisms, and as such is a promising target for anticancer therapy [22 , 26] .…”