Overexpression of fibroblast activation protein (FAP) in the stroma of proliferative inflammatory atrophy (PIA) and primary adenocarcinoma of the prostate.

Abstract

Fibroblast activation protein (FAP) is a serine protease upregulated at sites of tissue remodelling and cancer that represents a promising therapeutic and molecular imaging target. In prostate cancer, studies of FAP expression using tissue microarrays are conflicting, such that its clinical potential is unclear. Furthermore, little is known regarding FAP expression in benign prostatic tissues. Here we demonstrated, using a novel iterative multiplex immunohistochemistry assay in standard tissue sections, that FAP was nearly absent in normal regions ​but was increased consistently in regions of proliferative inflammatory atrophy (PIA). In carcinoma, FAP was expressed in all cases ​but was highly heterogeneous. High FAP levels were associated with increased pathological stage and cribriform morphology. We verified that FAP levels in cancer correlated with CD163+ M2 macrophage density. In this first report to quantify FAP protein in benign prostate and primary tumours, using standard large tissue sections, we clarify that FAP is present in all primary prostatic carcinomas, supporting its potential clinical relevance. The finding of high levels of FAP within PIA supports the injury/regeneration model for its pathogenesis and suggests that it harbours a protumourigenic stroma, yet ​high levels of FAP in benign regions could lead to false-positive FAP-based molecular imaging results in clinically localised prostate cancer.