Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas

Lung Cancer. 2009 Oct;66(1):64-74. doi: 10.1016/j.lungcan.2009.01.007. Epub 2009 Feb 6.


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 non-small cell lung carcinomas (NSCLC), as well as the involvement of the transcription factor FOXM1, that controls cell proliferation, in this process. Paraffin-embedded tissue sections of 80 NSCLC 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 NSCLC 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 NSCLC 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 NSCLC histological types and with nuclear GLI1 immunolocalization only in adenocarcinomas. Overexpression of FOXM1 in NSCLC was also significantly correlated with PTCH1, SMO and GLI1 expression. In conclusion, HH-signaling pathway is activated in NSCLC and correlates with histological type, prognostic parameters of the tumors as well as with the increased expression of FOXM1.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation
  • Female
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Smoothened Receptor
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli2


  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • GLI1 protein, human
  • GLI2 protein, human
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli2