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CENP‐F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer
Author(s) -
O'Brien Sallyann L.,
Fagan Ailís,
Fox Edward J.P.,
Millikan Robert C.,
Culhane Aedín C.,
Brennan Donal J.,
McCann Amanda H.,
Hegarty Shauna,
Moyna Siobhan,
Duffy Michael J.,
Higgins Desmond G.,
Jirström Karin,
Landberg Göran,
Gallagher William M.
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22413
Subject(s) - breast cancer , tissue microarray , oncology , biomarker , cancer , medicine , cohort , cancer research , biology , genetics
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.