Expression of p63, COX-2, EGFR and beta-catenin in smokers and patients with squamous cell carcinoma of the head and neck reveal variations in non-neoplastic tissue and no obvious changes in smokers

Int J Oncol. 2005 Dec;27(6):1661-7.


Squamous cell carcinoma of the head and neck (SCCHN), the 6th most common malignancy in the world, is associated with smoking and has a low 5-year survival rate. Various changes have been described at different stages of SCCHN tumour development, including overexpression of p63, a protein important for development of normal epidermal structures. p63 has been suggested to activate beta-catenin, and nuclear accumulation of beta-catenin is an important event in many cancers. Elevated COX-2 activity and overexpression of EGFR protein has been shown in a variety of human cancers, including SCCHN. An important question for the pathogenesis of SCCHN is when the genetic changes take place during the natural course of the disease, and whether they appear in clinically normal oral mucosa to predispose tumour development. We mapped the expression of p63, COX-2, EGFR, beta-catenin, and PP2A in oral mucosa from smokers/non-smokers and from patients with SCCHN. We also considered if changes occurring in tumours are present in the clinically normal tissue adjacent to the tumour. No direct influence of heavy smoking on the levels of the proteins studied could be seen. Tumours and clinically normal non-neoplastic tissue from SCCHN patients showed increased expression of COX-2 and PP2A. Interestingly, non-neoplastic tissue adjacent to SCCHN also showed increased beta-catenin, although this was not seen in tumours. The data support the notion that pre-existing alterations in clinically normal epithelium exist in patients with SCCHN and could be important for the pathogenesis of the disease and for local recurrences.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • DNA-Binding Proteins
  • ErbB Receptors / metabolism
  • Female
  • Genes, Tumor Suppressor
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mouth Mucosa / metabolism*
  • Phosphoprotein Phosphatases
  • Phosphoproteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking*
  • Trans-Activators / metabolism
  • Transcription Factors
  • Tumor Suppressor Proteins
  • beta Catenin / metabolism


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Membrane Proteins
  • Phosphoproteins
  • RNA, Messenger
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • beta Catenin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • ErbB Receptors
  • Phosphoprotein Phosphatases