Abstract P6-16-09: SPARC expression in brain metastases of breast cancer patients
Authors: Witzel Isabell , Matschke Jakob , Glatzel Markus , Milde-Langosch Karin , Laakmann Elena , Loibl Sibylle , Pfitzner Berit M , Denkert Carsten , Müller Volkmar 
Published: May 2015

Abstract
Background: The incidence of brain metastases in breast cancer patients is rising and has become a major clinical challenge in the last years with so far limited therapeutic options. Therefore, further insights into the biology of brain tropism are important. Secreted protein acidic and rich in cysteine (SPARC) is an albumin-binding protein. A differential expression of SPARC in breast tumor tissue and its surrounding stroma compared to normal tissues has been described and might be associated with poor prognosis. In this study, tissues of brain metastases were evaluated for SPARC expression by immunohistochemistry using a standardized immunoreactive score (IRS).
Methods: 138 tissue samples of brain metastases were available for construction of a tissue-microarray (TMA) and evaluation of SPARC expression. Immunohistochemical staining for SPARC was carried out as previously described (Sinn et al. Ann Onc, 2014) using the antibody Novocastra NCL-O-NECTIN; Clone: 15G12; 1:100). For stromal SPARC expression, the intensity of staining was evaluated by a four-tier scoring system (negative, weak, moderate and strong). Cytoplasmic SPARC expression was evaluated by the percentage of tumor cells with cytoplasmatic staining (0 % = "0", 1-10 % = "1", 11-50 % = "2", 51-80 % = "3", 81- 100 % = "4"). The staining intensity was evaluated as negative (0), weak (1), moderate (2) or strong (3). The numeric values were multiplied, resulting in an immunoreactivity score (IRS) ranging from 0 to 12. The definition for high cytoplasmic SPARC was IRS ≥ 3 (at least weak intensity in &gt; 50 % of tumor cells or at least strong intensity in 1-10 % of tumor cells). Staining of normal brain tissue and comparison to primary breast tumors is still ongoing.
Results: Cytoplasmic SPARC expression was detectable in 104 cases (78%), 30 cases were negative (22%). Stromal SPARC intensity was strong in 65 (63%) cases, moderate in 35 (34%) cases and low in 4 cases (4%). There was a weak association between stromal and cytoplasmic SPARC expression (r=0.22, p=0.010). No significant association between SPARC expression and clinicopathological parameters could be observed. 43.5% (n=54) of brain metastases were HER2-positive, 39.5% (n=49) were triple-negative and 16.9 % (n=21) were HR+/HER2 negative. Cytoplasmic SPARC expression was slightly higher in HER2 positive compared to triple-negative brain metastases. Regarding survival analysis, strong stromal SPARC expression was associated with shorter overall survival from first diagnosis of brain metastases but did not reach statistical significance (HR 4.2, 95%-CI 0.5 – 34, p=0.18).
Conclusion:
SPARC is frequently expressed in brain metastases of breast cancer patients. It might provide additional prognostic information in patients with brain metastases.
Citation Format: Isabell Witzel, Jakob Matschke, Markus Glatzel, Karin Milde-Langosch, Elena Laakmann, Sibylle Loibl, Berit M Pfitzner, Carsten Denkert, Volkmar Müller. SPARC expression in brain metastases of breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-16-09.