Annals of Oncology Advance Access originally published online on September 13, 2006
Annals of Oncology 2006 17(12):1797-1802; doi:10.1093/annonc/mdl310
© 2006 European Society for Medical Oncology
gynecologic tumors |
Automated quantitative analysis of DCC tumor suppressor protein in ovarian cancer tissue microarray shows association with ß-catenin levels and outcome in patients with epithelial ovarian cancer
1 Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece; Departments of
2 Medical Oncology and
3 Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
4 Histopathology Department, Alexandra Hospital, Athens, Greece
* Correspondence to: Dr A. Bamias, 31 Komninon Street, Haidari, 124 62 Athens, Greece. Tel: 030 210 3381546; Fax: 030 210 3381511; E-mail: abamias{at}med.uoa.gr
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 ß-catenin levels. Here, we sought to determine the association of DCC with ß-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 platinumpaclitaxel (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 ß-catenin, a significant relationship was found, where tumors with low DCC had low ß-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 ß-catenin levels.
Key words: ß-catenin, DCC, ovarian cancer, prognosis
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