GENETIC-EVIDENCE FOR AN INDEPENDENT ORIGIN OF MULTIPLE PRENEOPLASTIC AND NEOPLASTIC LUNG LESIONS

Patients with a primary cancer in the lung or in the upper aerodigesti ve tract have an increased risk of developing synchronous or metachron ous second primary lung tumors, This phenomenon has been related to th e chronic exposure of the bronchial tree to carcinogens through a so-c alled ''field cancerization'' process, This study was designed to inve stigate at the somatic level the genetic basis of the field cancerizat ion effect in patients having multiple simultaneous neoplastic and pre neoplastic lesions of the lung, The pattern of specific genetic change s occurring with high frequency and in early stages of lung carcinogen esis including p53 mutations, deletions of chromosome 3p, and K-ras mu tations, was investigated by immunocytochemical, cytogenetic, and mole cular approaches in 11 synchronous lesions of five patients with multi ple lung cancers, Different genetic lesions were observed in all of th e pathological specimens analyzed from each patient, The pattern of th ese changes was different both in topographically distant or adjacent lesions and in tumors with the same histopathological diagnosis suppor ting their independent origin. The present data provide further eviden ce of the clinical relevance of the field cancerization process, and s upport the use of genetic markers in the differential diagnosis of rec urrence or metastasis versus second primaries of the lung.