title: Overexpression of the Hedgehog signalling pathway in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Overexpression of the Hedgehog (HH) signalling pathway has been described in several malignancies and is associated with a poor prognosis. HH signalling blockade reduces tumour growth in vitro and in vivo. We aimed to determine whether head and neck squamous cell carcinomas (HNSCCs) express HH proteins in comparison to healthy mucosa.
  
  
  METHODS
  Formalin-fixed and paraffin-embedded tissue sections of 10 patients with HNSCC were stained with fluorescence-labelled antibodies for cytokeratin and HH proteins (SHH, PTCH1/2, SMO, Gli1-3) and photographs were taken with a laser scanning microscope. The pixel count and colour intensity were analysed in RGB (red/green/blue) colour mode, and expression levels were compared to healthy mucosa.
  
  
  RESULTS
  Image analysis in RGB mode provided objective evidence for the over-expression of HH signalling components in HNSCC, particularly with regard to the transcription factors Gli1 (10-fold) and SHH (5-fold) in comparison with healthy mucosa. The lowest levels were found for Gli3 in HNSCC.
  
  
  CONCLUSIONS
  We postulate pivotal roles of Gli1 and SHH expression in the carcinogenesis of HNSCC. HH pathway overexpression appears to be involved in the initiation of tumour growth and spread due to its stem cell-modulating properties. Detection of HH pathway components, and especially Gli1 and SHH, in HNSCC might offer a promising target for further anticancer research in HNSCC.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Germany.
authors.forename: Kamelia
authors.initials: K
authors.lastname: Dimitrova
authors.forename: Matthaeus
authors.initials: M
authors.lastname: Stoehr
authors.forename: Faramarz
authors.initials: F
authors.lastname: Dehghani
authors.forename: Andreas
authors.initials: A
authors.lastname: Dietz
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wichmann
authors.forename: Julia
authors.initials: J
authors.lastname: Bertolini
authors.forename: Christian
authors.initials: C
authors.lastname: Mozet
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D053823:Hedgehog Proteins