Clinical/prognostic significance of Syndecan-1 expression in invasive breast carcinoma with distant metastasis and its correlation with tumor immunity

Abstract

ObjectiveBreast Cancer (BC) is the most common malignant tumor for women in the world. 90% of BC-associated deaths are attributed to distant metastasis (DM). Therefore, there is an urgent need for a novel molecular target for the treatment of distant metastatic breast cancer (DMBC). Syndecan-1 (SDC-1) is a cell surface heparan sulfate proteoglycan (HSPG). This study aims to study the expression patterns of SDC-1 in invasive breast carcinoma (IBC) with DM and to analyze its relationship with different clinicopathologic features, stromal tumor infiltrating lymphocytes (sTILs) status and the clinical outcomes. MethodsA total of 50 DM breast cancer and 100 non-distant metastasis (non-DM) breast cancer patients in West China Hospital, Sichuan University from January 1, 2011 to December 31, 2011 were collected. Immunohistochemical (IHC) method was used to detect the expression of SDC-1, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 in 150 specimens of patients with IBC. STILs were used to evaluate immune cells in the stromal tissue within the tumor. Various clinicopathologic characteristics were retrospectively analyzed, and follow-up information were collected for prognosis analyses. The expression pattern difference of SDC-1 in the DM group and the non-DM group and its correlation with clinicopathologic characteristics of IBC were analyzed. ResultsCompared with the non-DM group, SDC-1 had higher cytoplasmic (90.0%) and stromal diffuse (70.0%) expressions and lower stromal peritumoral (18.0%) expression in the DM group. SDC-1 cytoplasmic expression was significantly associated with HER2-positive and high Ki-67 index in DM group, and with high histological grade and lymph node (LN) metastasis in non-DM group (P < 0.05). Compared with the non-DM group, the membranous expression of SDC-1 in the DM group was related to higher histological grade and T stage, higher frequency of LN involvement. Meanwhile, the expression pattern of SDC-1 in tumor stroma was associated with sTILs status (P < 0.05). The different combinations of SDC-1 staining patterns were correlated with clinicopathological features, biomarkers and sTILs status between DM group and non-DM group.There was no significant difference in overall survival between DMBC with different expression patterns of SDC-1. ConclusionThe cytoplasmic and stromal expressions of SDC-1 in the primary lesion of IBC are closely associated with DM, and the stromal expression of SDC-1 is correlated with tumor immune microenvironment. SDC-1 is expected to be a potential new marker for predicting the risk of DM in IBC.