Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumors.
Aberrant activation of the Wnt signaling pathway plays an important role in the development of solid tumors such as breast and colon cancer. Secreted Frizzled-related protein 1 (SFRP1) is a negative regulator of the Wnt pathway. It has been described that SFRP1 mRNA is strongly down-regulated in breast cancer and a putative tumor suppressor function has been postulated. We have generated and characterized an SFRP1 specific antibody to analyze its expression on protein level and to investigate the association of SFRP1 expression with clinicopathological parameters and patient survival. Analysis of >2000 invasive breast tumors and 56 carcinoma in situ revealed similar frequencies of SFRP1 loss in these tumors (46% and 43% respectively). Therefore, we propose that loss of SFRP1 expression is an early event in breast tumorigenesis. SFRP1 expression was inversely correlated with tumor stage (p<0.001) but not with tumor grade (p=0.14) or lymph node status (p=0.84). Performing a multivariate analysis we could confirm the association between tumor stage and SFRP1 expression (p=0.029). In particular, loss of SFRP1 expression in early stage breast tumors (pT1) was associated with poor prognosis (p=0.04). In conclusion, expression of SFRP1 is commonly lost in breast cancer. SFRP1 expression might be useful as a novel prognostic marker in early stage breast cancer.
Klopocki
Eva
E
Freie Universität Berlin, Berlin, Germany.
Kristiansen
Glen
G
Wild
Peter J
PJ
Klaman
Irina
I
Castanos-Velez
Esmeralda
E
Singer
Gad
G
Stöhr
Robert
R
Simon
Ronald
R
Sauter
Guido
G
Leibiger
Haike
H
Essers
Lutz
L
Weber
Birgit
B
Hermann
Klaus
K
Rosenthal
André
A
Hartmann
Arndt
A
Dahl
Edgar
E
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D000094742:Secreted Frizzled-Related Proteins
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins