RECURRENCES AND 2ND PRIMARY TUMORS IN THE HEAD AND NECK REGION - DIFFERENTIATION BY P53 MUTATION ANALYSIS

Background: Patients with head and neck cancer are at high risk of dev eloping additional primary tumours in the aerodigestive tract as a res ult of field cancerization phenomena. In this context, the appearance of a new neoplasm often poses a problem of differential diagnosis betw een recurrence and new primary tumour. The differentiation between the two entities is essentially clinical and conventionally based on the histological and spatio-temporal relations between the two lesions; ho wever, the validity of these criteria has still to be assessed. Design : To evaluate whether field cancerization phenomena may affect the cli nical diagnosis of relapse/metastasis in the head and neck region, p53 mutation pattern was analysed in a series of primary tumours and corr esponding recurrences/metastases. The rationale was that, since p53 mu tations are a very early and polymorphic phenomenon, a recurrence/meta stasis must retain the same mutation as the primary tumour, whereas in dependent tumours are likely to display a different p53 gene status. R esults:Molecular analysis provided conclusive results in 9 of 12 case analysed. The clinical diagnosis of recurrence was confirmed by molecu lar analysis in 4 of these cases. In contrast, a differential p53 muta tion pattern supported an independent origin for 3 presumed local recu rrences and 2 lung lesions. Conclusions: The use of p53 mutation analy sis as a clonality marker allowed us to ascertain the inadequacy of th e current diagnostic criteria for the differentiation between a new in dependent tumour and recurrence/metastasis. These findings substantiat e the relevance of field cancerization phenomena in the head and neck region and prompt the use of p53 mutation analysis as a fundamental to ol to improve the diagnosis and management of head and neck cancers.