C-ERBB-2 EXPRESSION AND CODON 12-K-RAS MUTATIONS BOTH PREDICT SHORTENED SURVIVAL FOR PATIENTS WITH PULMONARY ADENOCARCINOMAS

We evaluated the prognostic significance of p185c-er6B-2 expression and uas gene mutations in all patients diagnosed with a pulmonary adenocarcinoma between 1982 and 1985 at the University of Iowa. p185c-er6B-2 expression was detected in 15 cases (34%). A was gene mutation was found in 16 cases (36%) and all were in codon-l2 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 sis cases (14%). By univariate analysis p185c-er6B-2 expression was associated with shortened survival (P = 0.02) while the presence of a K-vas 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-er6B-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 Ii-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.