Prostate-derived Ets transcription factor overexpression is associated with nodal metastasis and hormone receptor positivity in invasive breast cancer.
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, and normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters and compared with hormonal receptor and HER-2/neu status and 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), and 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, and possible links with hormone receptors biology, bear great potential for new therapeutic avenues.
Turcotte
Simon
S
Laboratoire d'immuno-oncologie, Institut du cancer de Montréal, Centre de recherche du CHUM-Hôpital Notre-Dame, Montreal, Quebec, Canada.
Forget
Marie-Andrée
MA
Beauseigle
Diane
D
Nassif
Edgar
E
Lapointe
Réjean
R
D000368:Aged; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D050783:Proto-Oncogene Proteins c-ets / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C403974:SPDEF protein, human; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen