Bamias A, Yu Z, Weinberger P M, Markakis S, Kowalski D, Camp R L, Rimm D L, Dimopoulos M A, Psyrri A
Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece.
Ann Oncol. 2006 Dec;17(12):1797-802. doi: 10.1093/annonc/mdl310. Epub 2006 Sep 13.
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.
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).
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).
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.
