Y-Box-Binding Protein-1 Expression Is Associated with Suppressed E-Cadherin Levels and Poor Prognosis in Breast Cancer
T Ng, V Evdokimova, N Melnyk, P Sorensen. BC Cancer Research Centre, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada
Background: YB-1 is a transcription and translation regulatory DNA/RNA binding protein previously shown to be associated with cancer aggressiveness. We showed in unpublished in vitro data that YB-1 overexpression in the MCF-10A breast cell line results in suppression of proliferation in combination with a switch to a mesenchymal phenotype dependent on Ras overexpression. This is mediated at least in part through translational upregulation of Snail levels resulting in increased E-cadherin. We therefore wished to investigate this result in primary tumor tissue, and identify possible prognostic implications.
Design: Using a tissue microarray (TMA) consisting of 143 interpretable cases in duplicate cores of in situ and invasive breast cancer, with associated clinical follow-up data for 20 years, we performed immunohistochemistry (IHC) for YB-1 and E-cadherin. Immunofluorescence (IF) for the same markers was done on whole sections of normal breast tissue, ductal carcinoma in-situ (DCIS) and ductal carcinoma. YB-1 cytoplasmic and nuclear staining was scored separately (0-2+) while only membranous E-cadherin expression was scored (0-2+).
Results: Consistent with our in vitro data of MCF-10A cells without Ras overexpression, normal breast epithelium shows co-expression of YB-1 and E-cadherin by IF. However, far less co-expression was seen in invasive ductal carcinoma. Interestingly, several cases of DCIS showed disseminated tumor cells in subjacent stroma that were positive for YB-1 but negative for E-cadherin. The IHC of the TMA again showed a statistically significant inverse correlation between YB-1 and E-cadherin expression levels in 65% of breast cancer specimens (Fisher's exact test, p=0.033). There was no significant association between YB-1 expression alone and survival, and only a trend towards increased survival with high E-cadherin expression alone. However, compared to the cases with low YB-1/high E-cadherin, high YB-1/low E-cadherin expression strongly correlated with a significant decrease in breast cancer-related survival (p=0.0143).
Conclusions: These findings suggest that high YB-1 expression is associated with loss of E-cadherin in invasive and therefore potentially metastatic breast cancer cells, and is indicative of poor clinical outcome.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 40, Monday Morning