Abstract P4-12-11: Up-regulation of SPARC is associated with breast tumor progression and epithelial SPARC expression is correlated with poor survival and MMP-2 expression in patients with breast carcinoma

Abstract

Abstract Background: Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the process of tumor invasion and metastasis in many cancers. Matrix metalloproteinases (MMPs) degrade the extracellular matrix and participate in several key processes of invasion and metastasis. The aims of this study were to evaluate the potential involvement of SPARC in the progression of breast tumor and to determine its association with outcome variables and MMPs expression in patients with breast carcinoma (BC). Materials and Methods: SPARC expression was examined in 8 pairs of BC tissues and surrounding normal tissues at mRNA and protein levels by quantitative real-time PCR (qRT-PCR), RNAscope in situ hybridization (ISH), Western blotting, and immunohistochemistry techniques. Immunohistochemical staining of SPARC on tissue microarray was done in 26 normal breasts, 76 ductal carcinoma in situ (DCIS), and 198 BC samples. In addition, we performed immunohistochemical staining for MMP-2 and MMP-9 in BC. Results: SPARC expression at mRNA and protein levels by qRT-PCR and Western blotting was significantly increased in BC tissues compared to the surrounding normal tissues (p < 0.05 and p < 0.01, respectively). RNAscope ISH and immunohistochemistry of SPARC confirmed that SPARC expression was increased in BC tissues compared with their normal tissues and its expression was more pronounced in the stromal compartment than in epithelial compartment. SPARC expression was different among the normal, DCIS and BC groups and epithelial SPARC expression increased progressively from normal breast through DCIS to BC (p < 0.001). In patients with BC, high epithelial SPARC expression was associated with worse disease-free and overall survival (p = 0.002 and p = 0.048, respectively) and independently predicted worse disease-free survival (p = 0.002). Epithelial SPARC expression was significantly correlated with MMP-2 expression (p < 0.05). Conclusion: Our results suggest that up-regulation of SPARC contributes to breast tumor progression. SPARC expression may be a useful biomarker for the prognostic prediction in patients with BC. SPARC can control extracellular matrix degradation through up-regulation of MMP-2. Citation Format: Lee JS, Kim G-E, Park MH, Yoon JH. Up-regulation of SPARC is associated with breast tumor progression and epithelial SPARC expression is correlated with poor survival and MMP-2 expression in patients with breast carcinoma [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-11.