title: High c-erbB-3 protein expression is associated with shorter survival in advanced non-small cell lung carcinomas.
abstract: c-erbB-3 is a new member of the Type I growth factor receptor family that includes epidermal growth-factor receptor (also called c-erbB-1) and HER-2/neu (also called c-erbB-2). Frequency and significance of c-erbB-3 overexpression in lung cancers have not been reported previously. A series of 549 cases of primary lung carcinomas were immunostained with a monoclonal anti-human c-erbB-3 antibody (Clone RTJ.1) using formalin-fixed, paraffin-embedded archival tissue. Sharp membranous staining or punctate cytoplasmic staining was interpreted as positive and scored 0 (< 5% of tumor cells), 1 (5-9%), 2 (10-49%), or 3 (> or = 50%). Medical records were reviewed for clinical data, including stage and survival. Actuarial cumulative survival analysis with the Mantel-Cox test was performed on 443 cases that had a single primary site in the lung of pure non-small cell carcinoma (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) and that also had follow-up data for more than 3 months. In all stages, squamous cell carcinoma showed the greatest rate of high c-erbB-3 positivity (score, 3) (34/119; 28.6%), followed by adenocarcinoma (41/256; 15.9%) and large cell carcinoma (7/66; 10.6%). Patients with high c-erbB-3 expression (score, 3) survived for significantly shorter times than did patients with low c-erbB-3-expression (score, 0-2) in Stages III and IV (P = 0.002), but not in Stage I or II non-small cell lung carcinomas. In conclusion, high c-erbB-3 expression in advanced non-small cell lung carcinomas might be an adverse prognostic factor. This finding suggests that c-erbB-3 might be a potential target for molecular therapy in advanced non-small cell lung carcinomas.
authors.affiliation: Department of Pathology, School of Medicine, University of California at San Diego 92103, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Yi
authors.forename: D
authors.initials: D
authors.lastname: Harclerode
authors.forename: M
authors.initials: M
authors.lastname: Gondo
authors.forename: M
authors.initials: M
authors.lastname: Stephenson
authors.forename: R W
authors.initials: RW
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Younes
authors.forename: P T
authors.initials: PT
authors.lastname: Cagle
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D020893:Receptor, ErbB-3; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D020893:Receptor, ErbB-3