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

• Published in: Oncotarget Vol. 7; no. 24; pp. 35843 - 35852
• Main Authors: Yang, Mu, Liu, Fangfang, Higuchi, Kayoko, Sawashita, Jinko, Fu, Xiaoying, Zhang, Li, Zhang, Lanjing, Fu, Li, Tong, Zhongsheng, Higuchi, Keiichi
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 14.06.2016
• Subjects: Adult; Aged; Aged, 80 and over; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry - methods; Immunohistochemistry - statistics & numerical data; In Situ Hybridization, Fluorescence - methods; In Situ Hybridization, Fluorescence - statistics & numerical data; Kaplan-Meier Estimate; Lymphatic Metastasis; Macrophages - metabolism; Middle Aged; Prognosis; Proportional Hazards Models; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Research Paper; Serum Amyloid A Protein - biosynthesis; Serum Amyloid A Protein - genetics; macrophages; tumor marker; breast carcinoma; serum amyloid A; survival
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.8561

Serum 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. SAA 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. Immunohistochemistry 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. Our 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.