CLINICAL IMPLICATION OF SCREENING P53 GENE-MUTATIONS IN HEAD AND NECKSQUAMOUS-CELL CARCINOMAS

The role of the tumour-suppressor gene p53 in the tumorigenesis of hea d and neck cancer has been well established, but the clinical signific ance of p53 alteration is still unclear. A group of 50 patients with h ead and neck squamous cell carcinoma (HNSCC) were investigated for p53 alterations. DNA was extracted from fresh tumour samples and polymera se chain reaction/single-strand conformation polymorphism analysis was used to detect p53 gene mutations in the region from exon 5 to exon 9 . In addition, p53 protein overexpression was assessed by immunohistoc hemistry using the monoclonal antibody DO-7 on paraffin-embedded tissu e sections. p53 gene mutations were found in 45% and p53 protein expre ssion was detected in 61.2% of tumour samples. While p53 protein expre ssion was not correlated with any clinical factors, p53 gene mutations indicated local regional recurrences of HNSCC. The risk of locoregion al recurrence was significantly greater in patients with a p53 gene mu tation than in patients with the wildtype p53 gene (P = 0.001). Multiv ariate analysis confirmed p53 gene mutation to be an independently pre dictive factor for the tumour recurrence (P = 0.0064). When we analyse d p53 gene mutation in 12 patients with primary and recurrent tumours, we found that 4 patients (33.3%) had a different p53 gene mutation in the recurrent tumour from that in the original primary tumour. The re sults indicate that p53 gene mutations and not protein overexpression are valuable predictors for tumour recurrences and for differential di agnosis of a second primary HNSCC.