title: C-erbB-2 expression and codon 12 K-ras mutations both predict shortened survival for patients with pulmonary adenocarcinomas.
abstract: We evaluated the prognostic significance of p185c-erbB-2 expression and ras gene mutations in all patients diagnosed with a pulmonary adenocarcinoma between 1982 and 1985 at the University of Iowa. p185c-erbB-2 expression was detected in 15 cases (34%). A ras gene mutation was found in 16 cases (36%) and all were in codon-12 of K-ras. No N-ras mutations were identified. Both p185c-erbB-2 expression and a K-ras mutation were found only in codon-12 and present in six cases (14%). By univariate analysis p185c-erbB-2 expression was associated with shortened survival (P = 0.02) while the presence of a K-ras mutation was not (P = 0.16). Multivariate analysis by the Cox proportional hazards model, controlling for patient age and tumor stage, also continued to identify p185c-erbB-2 expression as an independent unfavorable prognostic factor (P = 0.01). In this model a K-ras mutation also approached significance as a poor prognostic indicator (P = 0.06). The impact of both p185c-erbB-2 expression and a K-ras mutation on survival was additive and highly significant (P = 0.004). This additive nature suggests that together these two markers identify a high-risk population of lung adenocarcinoma patients that may benefit from aggressive therapy.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City 52242.
authors.forename: J A
authors.initials: JA
authors.lastname: Kern
authors.forename: R J
authors.initials: RJ
authors.lastname: Slebos
authors.forename: B
authors.initials: B
authors.lastname: Top
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: D
authors.initials: D
authors.lastname: Lager
authors.forename: R A
authors.initials: RA
authors.lastname: Robinson
authors.forename: D
authors.initials: D
authors.lastname: Weiner
authors.forename: D A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000206:Actuarial Analysis; D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000367:Age Factors; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases