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.

• 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.

Nyckelord

Adult

Aged

Aged; 80 and over

Blotting; Western

Carcinoma; Squamous Cell/genetics/metabolism/*pathology

Cyclooxygenase 2/genetics/metabolism

DNA-Binding Proteins

Female

Genes; Tumor Suppressor

Head and Neck Neoplasms/genetics/metabolism/*pathology

Humans

Male

Membrane Proteins/genetics/metabolism

Middle Aged

Mouth Mucosa/*metabolism

Phosphoprotein Phosphatase

Phosphoproteins/metabolism

RNA; Messenger/genetics/metabolism

Receptor; Epidermal Growth Factor/metabolism

Reverse Transcriptase Polymerase Chain Reaction

Smoking

Trans-Activators/metabolism

Tumor Markers; Biological/genetics/*metabolism

Tumor Suppressor Proteins

beta Catenin/metabolism

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