title: Automated quantitative analysis of DCC tumor suppressor protein in ovarian cancer tissue microarray shows association with beta-catenin levels and outcome in patients with epithelial ovarian cancer.
abstract: BACKGROUND
  The deleted in colorectal cancer (DCC) protein, the product of DCC tumor suppressor gene, is frequently altered in cancer. Preclinical data demonstrate that DCC regulates beta-catenin levels. Here, we sought to determine the association of DCC with beta-catenin protein levels, clinicopathological parameters and patient outcome in ovarian cancer using a method of in situ compartmentalized protein analysis.
  
  
  METHODS
  A tissue array composed of 150 advanced-stage ovarian cancers, treated with surgical debulking and platinum-paclitaxel (Taxol) combination chemotherapy, was constructed. For evaluation of protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA).
  
  
  RESULTS
  One hundred and twelve patients (74%) had sufficient tissue for AQUA. The median follow-up time for the entire cohort was 33 months. Patients with low nuclear DCC expression had a 3-year progression-free survival (PFS) rate of 0% compared with 33% of those with high DCC expression (P = 0.0067). In multivariate analysis, low nuclear DCC expression level retained its prognostic significance for PFS. Between DCC and beta-catenin, a significant relationship was found, where tumors with low DCC had low beta-catenin and vice versa (P = 0.003).
  
  
  CONCLUSIONS
  Low nuclear DCC levels predict for poor patient outcome in epithelial ovarian cancer. DCC may exert its antitumor function, in part, through regulation of beta-catenin levels.
authors.affiliation: Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece. abamias@med.uca.gr
authors.forename: A
authors.initials: A
authors.lastname: Bamias
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.forename: P M
authors.initials: PM
authors.lastname: Weinberger
authors.forename: S
authors.initials: S
authors.lastname: Markakis
authors.forename: D
authors.initials: D
authors.lastname: Kowalski
authors.forename: R L
authors.initials: RL
authors.lastname: Camp
authors.forename: D L
authors.initials: DL
authors.lastname: Rimm
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: A
authors.initials: A
authors.lastname: Psyrri
mesh_terms: D001331:Automation; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D016163:Genes, DCC; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin