Site-specific expression of amine oxidases in breast cancer metastases

Abstract

We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase (p = 0.001), tumoral diamine oxidase (p = 0.003), stromal diamine oxidase (p = 0.047), and stromal monoamine oxidase B (p = 0.002) were differentially expressed in different metastatic sites. Bone metastases showed low expression of lysyl oxidase, tumoral diamine oxidase, and stromal diamine oxidase. We observed high expression of lysyl oxidase in brain metastases, tumoral diamine oxidase in liver metastases, stromal diamine oxidase in lung metastases, and stromal monoamine oxidase B in bone metastases. Lysyl oxidase positivity was associated with progesterone receptor negativity (p = 0.001), and monoamine oxidase A positivity was associated with human epidermal growth factor receptor-2 negativity (p = 0.003) and the luminal A subtype (p = 0.003). On univariate analysis shorter overall survival was associated with stromal diamine oxidase negativity (p = 0.008), especially in lung metastases (p = 0.025), and stromal monoamine oxidase B positivity (p < 0.001). Stromal monoamine oxidase B positivity was an independent prognostic factor for shorter overall survival in multivariate Cox analysis (hazard ratio, 4.069; 95% confidence interval, 1.649–10.04; p = 0.002). Finally, in metastatic breast cancer, amine oxidase-related proteins were differentially expressed in a manner specific to metastatic site, and stromal monoamine oxidase B expression was correlated with prognosis.