C-erbB-2 expression and codon 12 K-ras mutations both predict shortened survival for patients with pulmonary adenocarcinomas.

Kern JA, Slebos RJ, Top B, Rodenhuis S, Lager D, Robinson RA, Weiner D, Schwartz DA
J Clin Invest. 1994 93 (2): 516-20

PMID: 7906694 · PMCID: PMC293872 · DOI:10.1172/JCI117001

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.

MeSH Terms (26)

Actuarial Analysis Adenocarcinoma Age Factors Base Sequence Biomarkers, Tumor DNA, Neoplasm DNA Primers ErbB Receptors Female Genes, ras Humans Lung Neoplasms Male Molecular Sequence Data Multivariate Analysis Neoplasm Staging Point Mutation Polymerase Chain Reaction Prognosis Proportional Hazards Models Proto-Oncogene Proteins Proto-Oncogenes Receptor, ErbB-2 Risk Factors Survival Analysis Time Factors

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