P53 MUTATION, BUT NOT P53 OVEREXPRESSION, CORRELATES WITH SURVIVAL INHEAD AND NECK SQUAMOUS-CELL CARCINOMA

Survival in squamous cell carcinoma of the head and neck (HNSCC) was c ompared with overexpression and mutation of the p53 gene. Archival tis sue from 77 tumours was analysed for protein expression using immunohi stochemistry (IHC) with the monoclonal antibody Do-7, and for the pres ence of mutation in exons 5-8 using single-stranded conformation polym orphism (SSCP), followed by DNA sequencing in SSCP-positive cases. p53 expression was scored as high (>70% nuclei stained) in 25 (32%) tumou rs, as intermediate (10-70% nuclei stained) in 19 (25%) tumours and as low (<10% nuclei stained) in 33 (43%) tumours. Twelve (18%) tumours e xhibited gene mutation (ten missense and two nonsense mutations) and a n additional five tumours contained changes that could not result in a mino acid substitution or protein truncation. There was no correlation between gene expression and mutation, mutations being equally frequen t in tumours with either high (4/25), intermediate (4/19) or low prote in expression (4/33). Fifty-eight patients were eligible for survival analysis. There was a strong correlation between p53 mutation and caus e-specific survival; median survival among mutated cases was 12.5 mont hs compared with >160 months among non-mutated patients (P < 0.005). T here was no correlation between p53 overexpression and survival. The r esults suggest that p53 mutation status is an important prognostic fac tor in HNSCC, and that IHC analysis of protein overexpression is an in adequate measure of gene mutation in these tumours.