PUB060 Importance of Sonic Hedgehog Pathway as Prognostic Marker in Patients with Extensive Stage Small Cell Lung Cancer

Abstract

Recent studies have reported that the sonic hedgehog (Shh) signaling pathway plays a crucial role during tumorigenesis, angiogenesis and cellular differentiation in various malignancies including lung cancer. The aim of this study is to investigate the value of Shh pathway as prognostic markers in extensive stage small cell lung cancer (ES-SCLC) patients. We retrospectively analyzed the data of 36 patients with ES-SCLC between 2008 and 2012 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemistry was done for Gli1, Patched, Shh1, and Smo. We performed survival analysis to find out the prognostic impact of these markers. All the 36 patients were treated with platinum based doublet chemotherapy. Median progression free survival and median overall survival was 6.9 months (95% CI, 6.5-7.3) and 11.7 months (95% CI, 9.1-14.3), respectively. Overall response rate was 84%. Of the 36 specimens examined, the overexpression of Gli1, Patched, Shh, and Smo was found in 12 (33.3%), 5 (13.9%), 5 (13.9%), and 6 (16.7%), respectively. We found that high expression of Shh was associated with worse progression free survival (6.3 vs. 7.6 months, p<0.01) and overall survival (9.2 vs. 12.0 months), whereas other markers were not related to the prognosis of patients. To our knowledge, this is the first report of the relationship between components of the Shh signaling pathway and prognosis in SCLC. We found that a high proportion of tumors expressed proteins related to this pathway, and over-expression of Shh was correlated with worse survival in this analysis. Shh signaling in SCLC requires further investigation using a larger sample size.