The expressions of autotaxin-lysophosphatidate signaling-related proteins in metastatic breast cancer.

Purpose: We evaluated the expression of autotaxin-lysophosphatidate signaling-related proteins and the clinical implications for metastatic breast cancer.

Methods: We constructed tissue microarrays (TMA) with 126 cases of metastatic breast cancer [31 (24.6%) bone metastases, 36 (28.6%) brain metastases, 11 (8.7%) liver metastases, and 48 (38.1%) lung metastasis], and we conducted immunohistochemical staining for the autotoxin-lysophosphatidate signaling-related proteins ATX, LPA, LPA, and LPA.

Results: Stromal ATX (P = 0.006) and LPA (P < 0.001) were differently expressed according to their metastatic organ; stromal ATX showed high expression in bone metastasis, and LPA showed high expression in liver and lung metastases. Stromal ATX positivity was higher than others in luminal A type tumors (P = 0.035), and stromal LPA positivity was correlated with a high Ki-67 labeling index (LI) (P = 0.005). In univariate analysis, tumoral LPA negativity was correlated with shorter overall survival (OS) (P = 0.015) in metastatic breast cancer. When analyzed according to the metastatic sites, tumoral LPA negativity was correlated with shorter OS (P = 0.010) in lung metastasis, whereas stromal LPA negativity was correlated with shorter OS (P = 0.026) in brain metastasis. In multivariate Cox analysis, tumoral LPA negativity was an independent poor prognostic factor (HR = 2.311, 95% CI: 1.029-5.191, P = 0.043).

Conclusion: Among autotoxin-lysophosphatidate signaling-related proteins, stromal ATX was highly expressed in bone metastases, and LPA was highly expressed in liver and lung metastases. Tumoral LPA might be a prognostic factor in metastatic breast cancer.