title: Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma.
abstract: 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.
authors.affiliation: Divisione di Oncologia Medica I, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genoa, Italy. ardizzon@hp380.ist.unige.it
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: M A
authors.initials: MA
authors.lastname: Cafferata
authors.forename: M
authors.initials: M
authors.lastname: Paganuzzi
authors.forename: R
authors.initials: R
authors.lastname: Filiberti
authors.forename: P
authors.initials: P
authors.lastname: Marroni
authors.forename: M
authors.initials: M
authors.lastname: Neri
authors.forename: V
authors.initials: V
authors.lastname: Fontana
authors.forename: G
authors.initials: G
authors.lastname: Nicoló
authors.forename: L
authors.initials: L
authors.lastname: Perdelli
authors.forename: C G
authors.initials: CG
authors.lastname: Stampino
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: R
authors.initials: R
authors.lastname: Puntoni
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases