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

Cancer. 2001 Oct 1;92(7):1896-904.


Background: HER-2/neu tissue overexpression is found in nearly 15% of patients with nonsmall cell lung carcinoma and is reported to affect prognosis adversely in surgical series. However, the prognostic role of serum HER-2/neu oncoprotein, particularly in patients with advanced lung carcinoma, remains unknown. This study was designed to assess the potential value of measuring serum levels of HER-2/neu oncoprotein in predicting response to treatment and survival in patients with locally advanced and metastatic nonsmall cell lung carcinoma.

Methods: Baseline serum HER-2/neu levels (fm/mL) were studied using an enzyme-linked immunosorbent assay method in 84 patients with newly diagnosed, advanced 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 performance status of 1. Fifty patients (59.5%) had nonsquamous histology, and 34 patients (40.5%) had squamous cell carcinoma. Thirty-four patients (40.5%) had 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 performed 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/mL vs. 51.9 fm/mL, respectively). The overall survival rate was 42.5% at 1 year and 12% at 2 years, with a median survival duration of 10 months. At univariate analysis, high HER-2/neu serum levels were associated with an unfavorable 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 survival 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 independent predictive value of serum HER-2/neu concentration as a negative prognostic factor (P = 0.02).

Conclusions: High pretreatment levels of HER-2/neu oncoprotein are associated with an adverse prognostic impact on survival in patients with locally advanced or metastatic nonsmall cell lung carcinoma.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / blood*
  • Survival Analysis


  • Antineoplastic Agents
  • Receptor, ErbB-2