Hedgehog (Hh) Signaling is a Predictor of Clinical Outcome for Advanced Non- Small Cell Lung Cancer (NSCLC)
Objective: Lung cancer still remains the leading cause of cancer deaths in the world and it lacks validated
biomarkers to predict clinical outcome. The Hedgehog (Hh) pathway is critical for cell growth and differentiation. The
aim of our study was to evaluate the role of the Hh signaling in the prediction of clinical outcome for advanced
Methods: We determined the expression of Hh-related molecules including Ptch1 and Gli1 (nuclear and
cytoplasmic) by immunohistochemistry in histologic samples (biopsies and surgical specimens) of advanced NSCLC
patients. All the neoplastic area included 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 evaluated and scored as
follows: 0 (absent), 1+ (low), 2+ (medium) and 3+ (high).
Results: We analyzed 35 lung cancer histological samples, 18 adenocarcinomas and 17 squamous cell
carcinomas. Positivity of Gli1-cytoplasmic and Gli1-nuclear expression was 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 longer 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 significant increase in progression
Conclusion: At our best knowledge this represents the first study investigating the role of HH in NSCLC patients.
Our results suggest that the Hh pathway might play a major prognostic role in NSCLC with significant differences
between the histotypes.