DNA microarrays have the potential to classify
tumors according to their transcriptome. Tissue microarrays (TMAs) facilitate the validation of
biomarkers by offering a high-throughput approach to sample analysis. We reanalyzed a high profile
breast cancer DNA microarray dataset containing 96
tumor samples using a powerful statistical approach, between group analyses. Among the genes we identified was
centromere protein-F (CENP-F), a gene associated with poor prognosis. In a published follow-up
breast cancer DNA microarray study, comprising 295 tumour samples, we found that CENP-F upregulation was significantly associated with worse overall survival (p<0.001) and reduced
metastasis-free survival (p<0.001). To validate and expand upon these findings, we used 2 independent
breast cancer patient cohorts represented on TMAs.
CENP-F protein expression was evaluated by immunohistochemistry in 91 primary
breast cancer samples from cohort I and 289 samples from cohort II. CENP-F correlated with markers of aggressive
tumor behavior including ER negativity and high
tumor grade. In cohort I, CENP-F was significantly associated with markers of CIN including
cyclin E, increased
telomerase activity, c-Myc amplification and
aneuploidy. In cohort II, CENP-F correlated with VEGFR2, phosphorylated Ets-2 and Ki67, and in multivariate analysis, was an independent predictor of worse
breast cancer-specific survival (p=0.036) and overall survival (p=0.040). In conclusion, we identified CENP-F as a
biomarker associated with poor outcome in
breast cancer and showed several novel associations of
biological significance.