P53 EXON-5 MUTATIONS AS A PROGNOSTIC INDICATOR OF SHORTENED SURVIVAL IN NON-SMALL-CELL LUNG-CANCER

Inactivation of the tumour-suppressor gene p53 has been described as o ne of the most common molecular changes found in lung tumours. Our pur pose was to study the prognostic value of p53 alterations and to deter mine whether some specific mutation type in the p53 gene could be asso ciated with poor clinical evolution in non-small-cell lung cancer (NSC LC) patients. To this end, we studied 81 resected primary NSCLCs in or der to detect p53 alterations. p53 protein accumulation was analysed u sing immunohistochemistry methods; p53 gene mutations in exons 5-9 wer e studied using polymerase chain reaction-single-strand conformation p olymorphism and sequencing techniques. p53 protein was immunodetected in 46.9% of lung carcinomas and 44.7% of p53-immunopositive tumours sh owed p53 mutations. Survival analysis was performed on 62 patients. No survival differences were found for patients with or without p53 immu nopositivity. A shorter survival was found in patients with underlying p53 gene mutations, mainly in patients with squamous cell lung tumour s; the worst prognosis was found when mutations were located in exon 5 (P = 0.007). In conclusion, the location of p53 mutations might be co nsidered as a prognostic indicator for the evaluation of poor clinical evolution in NSCLC patients.