Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast

Abstract

Fibroblast activation protein (FAP)/seprase is a serine integral membrane proteinase with gelatinase activity, which is expressed by activated fibroblasts in the stroma of various epithelial cancers, mesenchymal tumors and breast-cancer cells, as well as during wound repair. However, the pathophysiologic significance of its expression remains poorly understood. The present study was designed to reveal the impact of stromal expression of FAP/seprase on survival in human breast cancer. Immunohistochemical expression of FAP/seprase was restricted to stromal fibroblasts adjacent to tumor-cell nests but not cancer cells, which was confirmed by double-labeling immunohistochemistry. Clinicopathologic analysis revealed that more abundant FAP/seprase expression in 112 cases of invasive ductal carcinoma is associated with longer overall and disease-free survival. Multivariate analysis with other clinicopathologic factors demonstrated that FAP/seprase expression is an independent prognostic factor. The effect on the survival rate of FAP/seprase was also apparent in cases with lymph node metastasis. FAP/seprase expression is one of the manifestations of the stromal reaction (i.e., matrix turnover); thus, invasive ductal carcinomas with fewer stromal reactions expressing FAP/seprase may be more aggressive.