Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

Abstract

Prostate-derived Ets transcription factor (PDEF) has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1). Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001), moderate to good differentiation (less than grade III, P = .01), dissemination to axillary lymph nodes (P = .002). PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002). It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001). Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

Keywords

• Prostate-derived Ets transcription factor (PDEF)
• Dikkopf-1 (DKKI)
• breast cancer
• expression profile
• tumor biomarkers