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. 2000 Jul 24;83(4):473–479. doi: 10.1054/bjoc.2000.1287

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

P M Schneider 1, H W Praeuer 3, O Stoeltzing 1, J Boehm 4, J Manning 5, R Metzger 1, U Fink 2, S Wegerer 2, A H Hoelscher 1, J A Roth 6
PMCID: PMC2374666  PMID: 10945494

Abstract

A prospective study was performed in patients with non-small cell lung cancer (NSCLC) to evaluate the prognostic importance of multiple molecular marker (p53, c-Ki-ras, c-erbB-2) testing. 103 patients with potentially curative resections (RO resection) for NSCLC in histopathological stages I–IIIA were included. SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes were performed on paired tumour and normal lung tissue samples and immunohistochemistry (c-erbB-2) was done on frozen tissue sections with a specific anti-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%) adenocarcinomas. Overexpression of c-erbB-2 (p185) was detected in 56/103 (54.4%) tumours. 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 one of the 3 parameters. In a regression model including a multiple molecular 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 appears 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. © 2000 Cancer Research Campaign

Keywords: lung cancer, tumour suppressor gene, p53, Ki-ras, c-erbB-2, prognosis

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Selected References

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