Expression of reactive oxygen species-related proteins in metastatic breast cancer is dependent on the metastatic site

Abstract

This study was performed to investigate the expression of reactive oxygen species (ROS)-related proteins and to analyze the implications for primary and metastatic breast cancer. We constructed a tissue microarray containing 143 metastatic breast cancers (52 lung metastases, 38 bone metastases, 37 brain metastases, and 16 liver metastases) and performed immunohistochemical staining for ROS-related proteins (catalase, GSTπ, TxNIP, and MnSOD). Analysis of ROS-related protein expression in metastatic breast cancers according to the metastatic sites revealed site-specific expression patterns. The expression of tumoral catalase was lower in bone metastases (P = 0.012), and stromal GSTπ expression was higher in bone and liver metastases (P < 0.001). The highest ROS activation status was observed for lung metastases, while non-activated ROS was observed for bone metastases (P = 0.001). Primary cancers were positive for stromal GSTπ, but a subset of lung metastases were negative (P = 0.021). Univariate analysis revealed that shorter overall survival (OS) was associated with negative catalase expression of the tumor (P = 0.026). Furthermore, univariate analyses according to the metastatic sites revealed that shorter OS was associated with TxNIP-positive tumors (P = 0.032) and the expression of stromal catalase (P = 0.032) in brain metastases. Tumors that were negative for MnSOD expression (P < 0.001) but positive for stromal catalase expression (P = 0.022) were associated with shorter OS in patients with liver metastases. In conclusion, cancer cells and stromal tissues showed different ROS-related protein expression patterns according to the metastatic site. In addition, the expression of ROS-related proteins is associated with patient prognosis.