Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma

BACKGROUND. HER-2/neu tissue overexpression is found in nearly 15% of patie nts with nonsmall cell lung carcinoma and is reported to affect prognosis a dversely in surgical series. However, the prognostic role of serum HER-2/ne u oncoprotein, particularly in patients with advanced lung carcinoma, remai ns unknown. This study was designed to assess the potential value of measur ing serum levels of HER-2/neu oncoprotein in predicting response to treatme nt and survival in patients with locally advanced and metastatic nonsmall c ell lung carcinoma. METHODS. Baseline serum HER-2/neu levels (fm/mL) were studied using an enzy me-linked immunosorbent assay method in 84 patients with newly diagnosed, a dvanced nonsmall cell lung carcinoma who underwent chemotherapy. RESULTS. The patients enrolled in the study included 76 males and 8 females , with a median age of 62 years (range, 36-73 years) and a median performan ce status of 1. Fifty patients (59.5%) had nonsquamous histology, and 34 pa tients (40.5%) had squamous cell carcinoma. Thirty-four patients (40.5%) ha d Stage III disease, and 50 patients (59.5%) had Stage IV disease. The mean baseline value of HER-2/neu in the whole series was 56.1 fm/mL (range. 13. 0-103.8 fm/mL). HER2 immunohistochemistry on paraffin embedded tissue was p erformed in 18 patients. HER-2/neu tissue overexpression was found in only one patient, who also showed high serum levels (102 fm/mL). No correlation was observed between protein serum quantitation and gender, age, histology, stage, performance status, leukocyte count, or smoking. Nonresponding and responding patients exhibited similar oncoprotein levels (median, 57.6 fm/m L vs. 51.9 fm/mL, respectively). The overall survival rate was 42.5% at 1 y ear and 12% at 2 years, with a median survival duration of 10 months. At un ivariate analysis, high HER-2/neu serum levels were associated with an unfa vorable survival outcome. Using a cut-off point for HER-2/neu of 73.0 fm/mL (corresponding to the 80th percentile of protein concentration), the survi val of patients who had higher serum levels of HER-2/neu was significantly worse compared with patients who had lower serum levels (median, 7.1 months vs. 10.9 months; P = 0.004). Multivariate analysis confirmed the independe nt predictive value of serum HER-2/neu concentration as a negative prognost ic factor (P = 0.02). CONCLUSIONS. High pretreatment levels of HER-2/neu oncoprotein are associat ed with an adverse prognostic impact on survival in patients with locally a dvanced or metastatic nonsmall cell lung carcinoma. (C) 2001 American Cance r Society.