SOX2 as a Potential Therapeutic Target in Squamous Cell Carcinoma of the Head and Neck
Maike Bode, Andreas Schrock, Petra M Bareiss, Friederike Goke, Alina Franzen, Robert Kirsten, Anne von Massenhausen, Tobias van Bremen, Friedrich Bootz, Glen Kristiansen, Claudia Lengerke, Sven Perner. Institution of Pathology, University Hospital of Bonn, Bonn, Germany; Institution of Otorhinolaryngology, University Hospital of Bonn, Bonn, Germany; Internal Medicine II, University Hospital of Tuebingen, Tuebingen, Germany
Background: Recently, we identified SOX2 as lineage specific oncogene in squamous cell carcinomas of the lung (LSCC). Since LSCC are morphologically and clinically related to head and neck squamous cell carcinomas (HNSCC), the aim of our study was to assess whether SOX2 amplification/over expression occurs in HNSCCs and if SOX2 could serve as a potential target for HNSCCs.
Design: We assembled a cohort of 503 patients with HNSCCs, including 260 metastases and 141 recurrences. All samples were assessed for SOX2 amplification by FISH and SOX2 expression by IHC. HPV status was detected by PCR-ELISA. Molecular parameters were correlated with each other and clinico-pathological data. Furthermore, SOX2 expression was modulated in the SCC25 HNSCC cell line via lentiviral vectors carrying shSOX2 and SOX2 over expression constructs to investigate the role of SOX2 in apoptosis resistance.
Results: 20% of primary HNSCCs displayed a SOX2 amplification and results in SOX2 over expression. In almost all cases, metastatic and recurrent tumor samples shared the same SOX2 amplification status as the corresponding primary tumor. SOX2 amplification/over expression was mutually exclusive with HPV infection. Amplification/over expression of SOX2 was significantly associated with pathological parameters of poor outcome. Efficient modulation of SOX2 gene and protein expression was obtained in the SCC25 cell line following treatment with lentiviral vectors. Inhibition of SOX2 expression enhanced apoptosis sensitivity of SCC25 cells to apoptosis-inducing agents while SOX2 over expression had the converse effect, inducing therapy resistance.
Conclusions: SOX2 amplification frequently occurs in primary HNSCC and is a clonal event in metastatic disease. Furthermore, SOX2 amplification/over expression is associated with worse prognosis, possibly related to enhanced therapy resistance of SOX2 expressing cells. Targeting SOX2 and related molecular pathways may enhance therapy efficacy in HNSCC. However, SOX2-amplified tumors could potentially comprise a subset of HNSCC against which may hold therapeutic efficacy.
Category: Head & Neck
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 212, Wednesday Morning