title: Expression of HER2neu (c-erbB-2) and epidermal growth factor receptor in cervical cancer: prognostic correlation with clinical characteristics, and comparison of manual and automated imaging analysis.
abstract: OBJECTIVE
  To evaluate HER2neu and epidermal growth factor receptor (EGFR) expression with respect to overall survival and disease-free survival (DFS), and correlate expression with pretreatment factors. Comparative evaluations of manual and automated immunohistochemical imaging systems for HER2neu and EGFR expression were made.
  
  
  METHODS
  Fifty-five patients with stages I-IVA carcinoma of the cervix were treated with definitive radiation therapy. Immunohistochemistry was performed for HER2neu and EGFR, and scored by both manual and automated methods. Univariate and multivariate analyses were performed with disease-free survival (DFS) and overall survival (OS) as primary endpoints, and biomarkers were evaluated for correlation between prognostic factors.
  
  
  RESULTS
  Strong correlations in HER2neu and EGFR protein expression were observed between digitally and manually analyzed staining (P <== 0.0001). Increased FIGO stage and decreased HER2neu expression were significant for reduced DFS on univariate analysis (P <== 0.001 and P = 0.03, respectively). Increased FIGO stage, decreased HER2neu expression, and increased membranous staining of EGFR were significant for diminished OS on univariate analysis (P <== 0.0001, P = 0.002, and P = 0.043, respectively). Multivariate analysis revealed only increased membranous staining of EGFR associated with diminished DFS and OS (P = 0.046 and P = 0.012, respectively). Overexpression of HER2neu correlated significantly with adenocarcinoma, and overexpression of EGFR correlated significantly with squamous cell carcinoma histology (P = 0.038 and P = 0.035). Inverse correlations were observed between HER2neu expression and clinical stage, EGFR membranous staining, and EGFR distribution (P = 0.007, P = 0.006, and P = 0.034, respectively).
  
  
  CONCLUSIONS
  Increased expression of HER2neu and decreased EGFR membranous staining identified patients with improved DFS and OS on univariate analysis, although only decreased EGFR membranous staining was significant on multivariate analysis. We also found strong correlation of results between manually and automated imaging methods.
authors.affiliation: Department of Radiation Oncology, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Lee
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Lee
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hammond
authors.forename: Alexander
authors.initials: A
authors.lastname: Tsodikov
authors.forename: Mark
authors.initials: M
authors.lastname: Dodson
authors.forename: Karen
authors.initials: K
authors.lastname: Zempolich
authors.forename: David K
authors.initials: DK
authors.lastname: Gaffney
mesh_terms: D000704:Analysis of Variance; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases