Abstract 3815: Stage I non-small cell lung cancer expressing SOX2 show more recurrence in elderly male patients with non-adenocarcinoma histology
Authors: Savic Spasenija , Zlobec Inti , Andreozzi Mariacarla , Schneider Sandra , Gugger Mathias , Lardinois Didier , Bubendorf Lukas , Tapia Coya 
Published: June 2012

Background: Around 30% of patients with early-stage non-small cell lung cancer (NSCLC) relapse after surgery. Therefore, new prognostic and predictive molecular markers are needed to identify patients who could benefit from adjuvant treatment. SOX2 (sex determining region Y-box 2) at the gene locus 3q26.33 is regarded as an oncogene involved in carcinogenesis of squamous cell lung carcinoma. Nevertheless, comprehensive data on SOX2 gene status and expression as well as its prognostic relevance in early-stage NSCLC are not yet available. The aim of the present study was to investigate the prevalence and the prognostic significance of SOX2 gene status and expression in a large series of stage I NSCLC patients.

Methods: A tissue micro array with 568 paraffin-embedded stage I NSCLC with comprehensive histopathological and clinical data, including follow-up on overall and tumor-specific survival was analyzed. SOX2 gene status was determined by fluorescent in situ hybridization (FISH) using direct-labeled BAC clones (SOX2: RP11-938O9; reference probe (RP): RP11-286G5). SOX2 gene status was recorded as follows: Amplification (ratio SOX2/RP ≥2.2), polysomy (more than 4 signals in the CEP or the gene probe) and normal (ratio: 0.8-1.8). Semi-quantitative expression of SOX2 protein was determined by immunohistochemistry (IHC). Any nuclear reaction of tumor cells was regarded as a positive result. FISH and IHC data were correlated with clinicopathological features and overall survival.

Results: An increased SOX2 gene number (amplification or polysomy) was observed in 4% of NSCLC (17/429). 94% of NSCLC (16/17) with an increased SOX2 gene number were observed in squamous- and large cell carcinomas (non-adenocarcionomas). Using logistic regression analysis an increased SOX2 gene number was significantly (p&lt;0.001) associated with SOX2 protein expression. SOX2 protein expression was detected in 48% of NSCLC and was significantly associated with a non-adenocarcinoma histology (p&lt;0.001): it was expressed in 78% of squamous cell carcinomas (178/227), in 35% of large cell carcinomas (12/34) and only in 15% of adeno-carcinomas (29/191). Significant associations with SOX2 protein expression were observed with high grade tumors (p&lt;0.001), elderly (&gt;50years; p=0.001) and male (p&gt;0.001) patients. Elderly male patients with non-adenocarcionoma histology and a smoking history expressing SOX2 had a tendency toward more recurrence (p=0.06).

Conclusions: An increased SOX2 gene number is rare in stage I NSCLC and it is mostly detected in squamous and large cell carcinomas. SOX2 protein expression stratifies a subgroup of NSCLC from elderly patients with a smoking history and non-adenocarcinoma histology. SOX2 two could become a potential therapeutic target molecule in a subgroup of patients with early stage NSCLC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3815. doi:10.1158/1538-7445.AM2011-3815