1663P - The role of Hedgehog (HH) signaling in the prediction of clinical outcome for advanced non-small cell lung cancer (NSCLC)

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Rossana Berardi
Authors R. Berardi1, A. Santinelli2, M. Caramanti1, A. Savini1, A. Onofri3, T. Biscotti2, A. Brunelli4, P. Mazzanti1, I. Bearzi5, S. Cascinu6
  • 1Clinica Di Oncologia Medica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT
  • 2Anatomia Patologica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, Ancona/IT
  • 3AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT
  • 4Thoracic Surgery, AOU Ospedali Riuniti Ancona, Ancona/IT
  • 5Anatomia Patologica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche,, Ancona/IT
  • 6Dipartimento Di Medicina Clinica E Biotecnologie A, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT

Abstract

Background

NSCLC lacks validated biomarkers to predict clinical outcome. 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 prognosis of NSCLC patients.

Methods

In this single-center prospective study, the expression of Hh-related molecules including Ptch1 and Gli1 (nuclear and cytoplasmic) was determined by immunohistochemistry in 35 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 considered and scored as 0 (absent), 1+ (low), 2+ (medium) and 3+ (high).

Results

We analyzed 18 adenocarcinomas and 17 squamous cell carcinomas. 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.

Conclusion

At our best knowledge this is the first study investigating the role of HH in NSCLC patients. The 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.

Disclosure

All authors have declared no conflicts of interest.