SOX2 Amplification Is a Frequent Event in Squamous Cell Lung Cancer
T Wilbertz, P Wagner, AC Stiedl, K Petersen, V Scheble, H Moch, NK Altorki, A Soltermann, S Perner. University Hospital Tuebingen, Tuebingen, Germany; New York Hospital/Weill Cornell Medical Center, New York, NY; University Hospital Zurich, Zurich, Switzerland
Background: Transcription factor SOX2 (3q26.3-q27) is a key regulator of pluripotency in embryonic stem cells and cooperates in the generation of induced pluripotent stem cells. In foregut development, SOX2 plays a critical role by maintaining cells in a pluripotent state. Recently, we found that SOX2 is amplified in about 30% of squamous cell lung and esophageal cancers (Bass et al. Nat Genetics. 2009). These findings suggest that SOX2 is activated by amplification as a lineage-survival oncogene. Activated SOX2 might return adult cells into a stemness state and thus participate in the carcinogenesis and progression of squamous cell lung carcinomas.
Design: Aim of our study was to verify SOX2 amplification and protein overexpression in non-small cell lung cancers (NSCLC). A total of 902 NSCLCs from two independent population-based cohorts (New York, NY: adenocarcinomas of the lung (ACL) n=298 ; squamous cell lung carcinomas (SCLC) n=48, and Zurich, Switzerland ACL: n= 243; SCLC: n=273) were assessed by fluorescence in-situ hybridization and immunohistochemistry. Within the SCLC cohort from Zurich, we assessed for association between SOX2 amplification and clinicopathologic features.
Results: In the New York cohort, 5.9 % of ACL and 60.4 % of SCLC showed a low level amplification of SOX2. High level amplification was found in 8.3 % of the SCLC samples. In the Zurich cohort, low level amplification was detected in 6.5 % of ACL and in 63 % of SCLC samples. 9.6 % of SCLC and 0.5 % of ACL exhibited a high level amplification of SOX2. SOX2 amplified cases had a significantly higher SOX2 expression compared to non-amplified samples. Within the Zurich cohort we found that high level SOX2 amplification was significantly associated with higher pN stage and an average gain of 20 cigarette packyears.
Conclusions: We could confirm frequent SOX2 amplification and overexpression in a large subset of NSCLCs. According to our findings, SOX2 amplification is highly specific for squamous differentiation. The clinical relevance of SOX2 amplification status needs to be further analyzed on independent cohorts.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 252, Tuesday Morning