Ο ρόλος του σηματοδοτικού μονοπατιού Sonic Hedgehog στον καρκίνο του πνεύμονα

Abstract

The hedgehog (HH)-signaling pathway is implicated in developmental processes and its aberrant activation in adult tissues has been associated with malignancy. The aim of this study was to determine the expression pattern of HH-signaling molecules in lung carcinomas, as well as the involvement of the transcription factor FOXM1, that controls cell proliferation, in this process. Paraffin-embedded tissue sections of 96 lung cancer cases and adjacent non-neoplastic lung parenchyma were immunohistochemically analyzed with anti-SHH, anti-Patched1 (PTCH1), anti-Smoothened (SMO), anti-GLI1, anti-GLI2 and anti-FOXM1 antibodies. Correlations of HH molecules with clinicopathological parameters and FOXM1 expression were evaluated. All the HH-signaling molecules examined were overexpressed in lung cancer compared with the adjacent non-neoplastic lung parenchyma. HH pathway activity and expression of PTCH1 and SMO were significantly higher in squamous cell carcinomas compared to other histological types. Activation of HH pathway and PTCH1 expression were correlated with tumor grade being higher in low grade tumors. There was a significant correlation of lymph node metastases with expression of SMO in all histological types and with the gender higher in men. Overexpression of FOXM1 in lung cancer was also significantly correlated with PTCH1, SMO and GLI1 expression. In conclusion, HH-signaling pathway is activated in lung cancer and correlates with histological type, prognostic parameters of the tumors as well as with the increased expression of FOXM1.