CENP‐F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer

Abstract

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. © 2006 Wiley‐Liss, Inc.

Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer

“…DNA microarrays and TMAs have also revealed that the upregulation of CENPF is significantly associated with a high tumor grade, a worse overall survival and a reduced metastasis-free survival in patients with primary breast cancer (17,25). Our present data indicated that the upregulation of CENPF mRNA expression was associated with a higher GS, an advanced pathological stage, the presence of metastasis, a shorter overall survival and PSA failure.…”

“…It has been demonstrated that CENPF is upregulated in primary breast cancer (25). As for hepatocellular carcinoma (HCC), CENPF has been found to be overexpressed in tumor tissue compared with non-tumor tissue (26).…”

Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F

“…Elevated Cenp-F expression has been associated with poor prognosis in patients with breast cancer, leading to the suggestion that Cenp-F overexpression might contribute to tumorigenesis (O'Brien et al, 2007). Surprisingly, we observed no obvious mitotic or cell-cycle defects following overexpression of various non-degradable Cenp-F mutants (data not shown) and as such the role of Cenp-F degradation remains unclear.…”

Microarray gene expression profiling in meningiomas: Differential expression according to grade or histopathological subtype

“…This molecule has also been described as a biomarker associated with poor outcome in breast cancer (52). MMP9, a component of the extracellular matrix, has been shown to be upregulated in atypical and anaplastic meningiomas (18,53) and has been proposed as a potential target for therapy in meningiomas (54).…”