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
N. Ariga et al., 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, INT J CANC, 95(1), 2001, pp. 67-72
Fibroblast activation protein (FAP)/seprase is a serine integral membrane p
roteinase with gelatinase activity, which is expressed by activated fibrobl
asts in the stroma of various epithelial cancers, mesenchymal tumors and br
east-cancer cells, as well as during wound repair. However, the pathophysio
logic significance of its expression remains poorly understood. The present
study was designed to reveal the impact of stromal expression of FAP/sepra
se on survival in human breast cancer. Immunohistochemical expression of FA
P/seprase was restricted to stromal fibroblasts adjacent to tumor-cell nest
s but not cancer cells, which was confirmed by double-labeling immunohistoc
hemistry. Clinicopathologic analysis revealed that more abundant FAP/sepras
e expression in 112 cases of invasive ductal carcinoma is associated with l
onger overall and disease-free survival. Multivariate analysis with other c
linicopathologic factors demonstrated that FAP/seprase expression is an ind
ependent prognostic factor. The effect on the survival rate of FAP/seprase
was also apparent in cases with lymph node metastasis. FAP/seprase expressi
on is one of the manifestations of the stromal reaction (Le., matrix turnov
er); thus, invasive ductal carcinomas with fewer stromal reactions expressi
ng FAP/seprase may be more aggressive. (C) 2001 Wiley-Liss, Inc.