Relationship Among Tumor Associated Macrophages And The Expression Of Secreted Protein Acidic And Rich In Cysteine (SPARC) And Its Significance In Breast Cancer

Purpose:to compare the infiltration of tumor-associated macrophages (TAMs) in breast cancer with that of M2 TAMs, and count the positive cells, detection the expression of SPARC in breast cancer, analyze the relation between TAMs, M2 TAMs and SPARC with clinical pathological characteristics and prognosis of breast cancer, and discuss biological significance of the infiltration of TAMs, M2 TAMs and the expression of SPARC in breast cancer.Method:1. Immunohistochemistry technique was used to examine the expression of CD68, CD206, stabilin-1 and the SPARC in 153 cases of breast cancer tissue and 30 cases of benign breast lesion.2. Immunofluorescence method was used to examine the co-expression of CD68/CD206, CD68/stabilin-1 and CD206/stabilin-1 in 20 cases of breast cancer tissue. The relationship between the expression of CD68, CD206, stabilin-1 and SPARC and clinical pathological characteristics was observed and analyzed.Results:1. The invasive density of CD68+macrophages in benign breast lesion was significantly lower than that in breast cancer tissue (P<0.001). The dense density of CD68+TAMs in breast cancer is correlated with negative expression of ER, PR expression and with high expression of Ki-67 (P=0.009, P=0.007, P=0.003). The infiltration density of TAMs in the four molecular subtypes of breast cancer is different (P=0.02). The infiltration density was irrelevant with age, histological grade, tumor size, lymph node staging and HER-2 expression status.2. The infiltration density of M2 TAMs in benign breast lesions was significantly lower than that in breast tissue (P<0.001). The dense-density infiltration of M2 TAMs was correlated with tumor size and lymph node in breast cancer (P=0.001, P=0.017); and was correlated with the negative expression of ER PR and the positive expression of HER-2 and higher expression of Ki-67 (P=0.001, P=0.025, P=0.024, P=0.014). The infiltration density of M2 TAMs in the four molecular subtypes of breast cancer is different (P=0.009). The infiltration density of M2 TAMs was irrelevant with age and histological grade (P>0.05).3. The invasive density of stabilin-1+TAMs in benign breast tissue was significantly lower than that in breast cancer tissue (P<0.001). The dense density of stabilin-1+ TAMs in breast cancer was correlated with tumor size, lymph nose staging and clinical staging (both P<0.001). The invasive density of stabilin-1+TAMs was uncorrelated with age, histological staging and hormone expression status (both P> 0.05).4. The expression of SPARC in benign breast lesion was significantly higher than that in breast cancer tissue (P=0.003). The expression of SPARC in breast cancer was correlated with lymph node stage and clinical stage (P<0.001, (P=0.001). while the expression of SPARC was uncorrelated with age, histological grade and hormone expression status (both P> 0.05). There was no relationship between the expression of SPARC with the invasive density of TAMs (r=0.039, P=0.632), while there was apparently negative correlation between SPARC with M2 TAMs (r=-0.268, P=0.001) and SPARC with stabilin-1+TAMs (r=-0.241, P=0.003).5. Immunofluorescence:All CD206+TAMs co-expressed CD68; only about 50 percent of CD68+TAMs co-expressed CD206. All stabilin-1+TAMs co-expressed CD68, while only about 30 percent of CD68+TAMs co-expressed stabilin-1. All stabilin-1+TAMs co-expressed CD206, while only about 65 percent of CD206+TAMs co-expressed stabilin-1. The invasive density of M2 TAMs and TAMs was positively correlated (r= 0.246, P=0.002). The invasive density of stabilin-1+TAMs and TAMs was uncorrelated (r= 0.149, P=0.066), while it was apparently correlated with M2 TAMs (r= 0.521, P<0.001).6. Survival analysis:High-density infiltration of M2 TAMs was correlated with decreased disease-free survival (DFS) and overall survival (OS) (P=0.020, P=0.005), while the infiltration density of TAMs, stabilin-1+TAMs and the expression of SPARC was irrelevant with them (both P>0.05).Conclusion:1. There was dense infiltration of macrophages in breast cancer tissue, and almost half of it was M2 TAMs. High-density infiltration of M2 TAMs could be likely to indicate poor prognosis of breast cancer.2. stabilin-1+TAMs may be a subtype of M2 TAMs.3. SPARC may be a biological marker to identify the clinical and lymph node stage and polarization of macrophages in breast cancer, and it may make influence with macrophages together.