Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non small cell lung cancer

A prospective study was performed in patients with non-small cell lung canc er (NSCLC) to evaluate the prognostic importance of multiple molecular mark er (p53, c-Ki-ras, c-erbB-2) testing. 103 patients with potentially curativ e resections (RO resection) for NSCLC in histopathological stages I-IIIA we re included. SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes we re performed on paired tumour and normal lung tissue samples and immunohist ochemistry (c-erbB-2) was done on frozen tissue sections with a specific an ti-c-erbB-2 monoclonal antibody. 46/103 (44.6%) NSCLC showed p53 mutations and 17/103 (16.5%) c-Ki-ras mutations including 12/37 (32.4%) adenocarcinom as. Overexpression of c-erbB-2 (p185) was detected in 56/103 (54.4%) tumour s. 24/103 (23.3%) NSCLC were negative for alterations in all 3 parameters ( c-Ki-ras, p53 and p185) whereas 79/103 (76.7%) were positive for at least o ne of the 3 parameters. In a regression model including a multiple molecula r marker parameter (negative for all 3 markers versus positive for at least one marker), histopathological stage (P < 0.00001), respectively the pT (P < 0.01) and pN (P < 0.00001) categories and the multiple molecular marker parameter (P < 0.01) were of significant prognostic importance. This study demonstrates that testing 3 molecular markers (c-Ki-ras, p53 and c-erbB-2) improves estimation of prognosis compared to single marker testing and appe ars to define low (82.6% +/- 7.9% 5-year survival) and high risk (40.2% +/- 5.5% 5-year survival) groups for treatment failure in potentially curative (RO) resected NSCLC. (C) 2000 Cancer Research Campaign.