Prognostic and predictive value of hedgehog (Hh) signaling in advanced non-small cell lung cancer (NSCLC).

Abstract

e21070 Background: Advanced NSCLC still represents a medical challenge in cancer therapy. The Hh pathway is critical for cell growth and differentiation. The aim of our study is to evaluate the role of the Hh signaling pathway in determining the clinical outcome of NSCLC patients. Methods: The expressions of Hh-related molecules including Ptch1 and Gli1 (nuclear and cytoplasmic) were determined by immunohistochemistry in 35 histologic samples (biopsies and surgical specimens) of advanced NSCLC patients. All the neoplastic area presents in the slides was considered and both cytoplasmic and nuclear stainings were evaluated, according to the positive neoplastic cells. The intensity of the staining was considered and scored as 0 (absent), 1+ (low), 2+ (medium) and 3+ (high). Results: 18 adenocarcinomas and 17 squamous cell carcinomas were analysed. Positivity of Gli1-cytoplasmic expression and Gli1-nuclear expression were expressed in adenocarcinoma at a significantly higher level and more frequently than compared to squamous cell carcinoma (p<0.05), while Ptch1 did not differ significantly in the two histotypes. Overall survival was higher in Gli1 and Ptch1 negative tumor samples compared to the positive group (p=0.02). The 18 patients with adenocarcinoma received erlotinib as second line therapy and those presenting a lower Gli1 and Ptch1 expression experienced a significantly better progression free survival. Conclusions: These results suggest that the Hh pathway might play a major prognostic role in NSCLC with significant differences between the histotype. Furthermore it might predict the efficacy of erlotinib as second-line treatment in patients with advanced lung adenocarcinoma.