B16: Loss of secreted frizzled-related protein-1 expression in breast cancer is associated with a characteristic lipid profile, lymph node positivity, hormone receptor negative status and a worse prognosis of the patients
1Department of Pathology, Anatomy and Tumour Biology, Leeds Institute of Cancer and Pathology, School of Medicine, Leeds, UK,2Charite University, Pathology Department, Berlin, Germany,3VTT Technical Research Centre of Finland, Espoo, Finland
Breast cancer is the most common cancer in women (Jemal et al, 2011). The lipidome of breast cancer can be used to define subtypes of breast cancer with varying patient prognoses (Brockmoller et al, 2012; Denkert et al, 2012; Hilvo et al, 2011). These changes in metabolism were transferred to the level of the regulatory proteins where secreted frizzled-related protein-1 (SFRP-1) an regulator of lipid metabolism showed promising results(Caldwell et al, 2004). The aim of this study was to further investigate the SFRP-1.
SFRP-1 staining (SFRP-1: Abcam, catalogue no. ab4193) was performed for 231 patients with primary breast cancer. The stains were digitised (Mirax, Scan; Zeiss, Jena, Germany, blind-evaluated (VMscope, Berlin, Germany) and the results were statistically analysed (version 18.0; SPSS, Inc., Chicago, IL, R). A weak (IRS of 0-4) or strong SFRP-1 (IRS of 6-12) expression group was different. The RNA expression of SFRP-1 was evaluated with a second independent dataset (Gyorffy et al, 2010). The results of the immunohistochemical analysis were correlated with the lipidomic (UPLC-MS, Medes et al. 2007, Hilvo et al 2011) data of corresponding fresh-frozen samples.
Low cytoplasmatic expression SFRP-1 IRS 0-4 (81.8%) showed a significant correlation with nodal status (p=0.054), hormone receptor (p=0.00023) and the molecular subtypes (p=0.0027). A low expression of SFRP-1 in the RNA data showed a significantly worse prognosis for the patients (p=0.031, n=514; www.kmplot.com; Gyorffy et al, 2010). All together 22 lipids were significantly altered lipids with respect to SFRP-1 low and high expression. From the identified lipids PC (18:2/18:0) was the only lipid which was up-regulated, and the following lipids were down regulated: TG(42:0), TG(56:5), TG(56:7), TG(56:8), TG(56:9), TG(58:10), TG(58:8) and TG(58:9)
Low SFRP-1 expression has a worse patient prognosis (mRNA) and is significantly correlated with nodal positive status, hormone receptor negative status, and molecular subtype (Ugolini et al, 2001) which is in keeping with previous studies (Klopocki et al, 2004). Promoter methylation of SFRP-1 is a common event in breast cancer and can provide constructive Wnt signalling (Suzuki et al, 2004; Veeck et al, 2006). An increase in one of the de novo synthesise lipids PC (18:2/18:0) could mean that SFRP-1 down regulation effects the regulation of de novo lipid synthesis in breast cancer.