P53 EXPRESSION IN NON-SMALL-CELL LUNG-CANCER - CLINICAL AND BIOLOGICAL CORRELATIONS

p53 is a tumor suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of ce llular growth. Mutations in p53 gene are the most common genetic alter ations in a several human cancers, including Non Small Cell Lung Cance r (NSCLC). However, up to now, the role of p53 in the tumour's behavio ur and its progression has not been completely clear. We performed imm unohistochemical staining for mutated p53 using two monoclonal antibod ies, PAb1801 and PAb240, in fresh tumour specimens from 103 consecutiv e patients who underwent surgery for resectable NSCLC. PAb1801 detects both the normal and mutant form of p53, while PAb240 is specific only for the mutant form and recognizes a denaturation-resistant epitope l ocated between aminoacids 156-335. Both antibodies showed a mainly nuc lear staining in neoplastic cells but not in surrounding uninvolved lu ng tissues. 68 out of 100 (68%) and 37 out of 103 (35.9%) of the cases were positive with PAb1801 and with PAb240, respectively. Tumours fro m patients with hilar-mediastinal lymph node involvement showed a high er p53 expression, detected by PAb1801, than those without nodal metas tases (p=0.04). Moreover, tumours expressing more than 60% of positive cells with both antibodies showed a significant increase of nodal inv olvement (p=0.1; p=0.03). Furthermore, p53 expression was significantl y related to post-surgical stage (p Tumor Stage) (p=0.04). In addition , we did not find any correlation between p53 expression and prolifera ting activity evaluated by PCNA, Ki-67 and DNA flow cytometric cell cy cle. In conclusion, the evaluation of p53 oncogene expression may iden tify individuals whose resectable NSCLCs have a more aggressive tumour behaviour.