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.
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.
Bamias
A
A
Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece. abamias@med.uca.gr
Yu
Z
Z
Weinberger
P M
PM
Markakis
S
S
Kowalski
D
D
Camp
R L
RL
Rimm
D L
DL
Dimopoulos
M A
MA
Psyrri
A
A
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*
D051176:beta Catenin