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 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.
Schneider
P M
PM
Department of Visceral and Vascular Surgery, University of Cologne, Germany. Paul.Schneider@Medizin.Uni-Koeln.de
Praeuer
H W
HW
Stoeltzing
O
O
Boehm
J
J
Manning
J
J
Metzger
R
R
Fink
U
U
Wegerer
S
S
Hoelscher
A H
AH
Roth
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism; D012307:Risk Factors
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D018719:Erb-b2 Receptor Tyrosine Kinases