Loss of SFRP1 is associated with breast cancer progression in early stage tumors

Freie Universität Berlin, Berlin, Germany.
International Journal of Oncology (Impact Factor: 3.03). 10/2004; 25(3):641-9. DOI: 10.3892/ijo.25.3.641
Source: PubMed


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.

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    • "Intermediate " v.s. " Poor " Among these ten genes, six of them, GDF5, TCF7L1, PAPSS1, SFRP1, GABRP, TGFB1, have been previously studied and verified in the literature that are associated with the breast cancer (See Margheri et al. (2012), Shy et al. (2013), Xu et al. (2012), Klopocki et al. (2004), Zafrakas et al. (2006), and Ghellal et al. (2000), respectively). Take for example GDF5 and TCF7L1, the overproduction of Transforming growth factor beta-1 (TGFβ), a multifunctional cytokine, is an important characteristic of late tumor progression. "
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    • "Immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE-) 4 μm TMA sections of tumour tissue specimen transferred to glass slides. TMA construction was performed as described previously [24,25]. TMAs were stained with monoclonal mouse anti-MTUS1 antibody (Abnova, Heidelberg/Germany, overnight, RT). "
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    • "They showed that mammary epithelial cells from SFRP1 knock-out mice had a decreased expression of p53, caspase-3, along with lesser DNA fragmentation in response to DNA damage and a recombinant expression of SFRP1 could elevate the levels of pro-apoptotic and p53 mediated gene expression. In another study, loss of SFRP1 expression was thought to be an early event in breast tumourigenesis [57], with its expression inversely correlated with tumour stage (p<0.001) but not tumour grade or lymph node status. "
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