The relationship between allelic imbalance on 17p, p53 mutation and p53 overexpression in head and neck cancer

The huge majority of head and neck squamous cell carcinoma (HNSCC) show alt erations of p53 either on the genetic level or on the protein level. Alleli c imbalance (AI)/ loss of heterozygosity (LOH) on 17p at the p53 locus is f requent in HNSCC. However, the complex relationship between these phenomena is poorly understood in HNSCC. We investigated one group of 39 HNSCC for: a) allelic imbalance on 17p using 4 microsatellite markers located througho ut this chromosomal arm; b) mutations of p53 in exons 5-9; and c) overexpre ssion of p53 using two antibodies located on opposite ends of the protein. AI/LOH was detected in 44% at the locus TP53, rising to 69% when regarding all 4 markers on 17p. Therefore, our data are in line with the assumption o f additional tumour suppressor genes on 17p in HNSCC. A nuclear accumulatio n of p53 (51%) was independent from the antibody and the recognised epitope . At the first glance there was no correlation between overall p53 mutation (36%) and overexpression. However, it appeared that, with very few excepti ons, only nonsense mutations did not lead to p53 overexpression, while miss ense mutations did. As overexpression of p53 was 15% more frequent than p53 mutations and only 35% of the rumours with p53 overexpression carried a p5 3 mutation, our data support the hypothesis of additional mechanisms of p53 overexpression. AI/LOH at the p53 locus in 83% of all tumours with a p53 m utation is in line with Knudson's theory of inactivation of tumour suppress or genes.