Serum amyloid A expression in the breast cancer tissue is associated with poor prognosis.

Mu Yang,Zhongsheng Tong,Lanjing Zhang,Jinko Sawashita,Fangfang Liu,Keiichi Higuchi,Li Zhang,Kayoko Higuchi,Li Fu,Xiaoying Fu

doi:10.18632/oncotarget.8561

Abstract

BackgroundSerum amyloid A (SAA), an acute-phase protein, is expressed primarily in the liver, and recently found also expressed in cancer tissues. However, its expression and prognostic value in breast cancer have not been described.ResultsSAA protein was found expressed in tumor cells in 44.2% cases and in TAM in 62.5% cases. FISH showed more frequent SAA mRNA expression in TAM than in tumor cells (76% versus 12%, p < 0.001), and a significant association between the frequencies of SAA mRNA expression in TAM and tumor cells (rs = 0.603, p < 0.001). The immunoreactivities of SAA protein in TAM and tumor cells were both associated with lymphovascular invasion and lymph node metastasis. Moreover, SAA-positivity in TAMs was associated with larger tumor-size, higher histological-grade, negative estrogen-receptor and progesterone-receptor statuses, and HER-2 overexpression. It was also linked to worse recurrence-free survival in a multivariable regression model.MethodsImmunohistochemistry was applied on the tumor tissues from 208 breast cancer patients to evaluate the local SAA-protein expression with additional CD68 stain to identify the tumor-associated macrophage (TAM) on the serial tissue sections. Fluorescent in situ hybridization (FISH) was conducted on serial tissue sections from 25 of the 208 tumors to examine the expression and location of SAA mRNA.ConclusionsOur results suggested that the TAMs may be a pivotal and main source of SAA production in tumor microenvironment of breast cancer. SAA immunoreactivity in TAM is associated with worse recurrence-free survival, and is therefore a biomarker candidate for postoperative surveillance and perhaps a therapeutic target for breast cancer.

Highlights

Serum amyloid A (SAA), a positive acute-phase protein, is generated primarily by the liver in response to trauma, infection, inflammation, and even neoplastic stimuli
Among the 208 invasive breast cancer samples, SAA protein was found expressed in tumor cell in 44.2% (92/208) cases (Figure 1A–1C) and expressed in macrophage in 62.5% (130/208) cases (Figure 1D–1F)
fluorescent in-situ hybridization (FISH) showed that SAA mRNA was predominantly located in tumor-associated macrophage (TAM) (76%, 19/25), and was detected in some infiltrating lymphocytes

Summary

Introduction

Serum amyloid A (SAA), a positive acute-phase protein, is generated primarily by the liver in response to trauma, infection, inflammation, and even neoplastic stimuli. SAA1 and SAA2 each consist of 122 amino acids, including signal peptide sequences, and share more than 90% of their amino acid sequences [2]. The production of SAA1 and SAA2 by hepatocytes is 100- to 1000-fold upregulated during the acute phase response. SAA is present in various forms, including SAA1 and SAA2 [3]. Serum amyloid A (SAA), an acute-phase protein, is expressed primarily in the liver, and recently found expressed in cancer tissues. Its expression and prognostic value in breast cancer have not been described

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