High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis

Abstract

-An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85–90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07–2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13–3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.

Expression levels of seprase/FAPα and DPPIV/CD26 in epithelial ovarian carcinoma

“…Furthermore, this process degrades local extracellular matrix components that are required for cell migration and matrix invasion during tumor invasion, angiogenesis and metastasis (21). Previous studies have revealed that seprase overexpression was evident in stromal fibroblasts and tumor cells in invasive breast, gastric, colonic and cervical carcinomas; however, it was absent or undetectable in all normal tissue cells, with the exception of cells involved in the early stages of wound healing (22)(23)(24)(25). In addition, an in vivo study using a mouse model of human breast cancer, demonstrated that seprase increased microvessel density and promoted rapid tumor growth (26).…”

Functional subsets of mesenchymal cell types in the tumor microenvironment

“…Prominent presence of CAF FAP in the stroma of solid tumors is correlated to a poor prognosis in colon carcinoma and pancreatic adenocarcinoma [26,27] …”

Transcriptional Regulation of Seprase in Invasive Melanoma Cells by Transforming Growth Factor-β Signaling

“…Specifically, seprase is up-regulated in infiltrating ductal carcinomas of the breast and in resulting tumor metastases (19) as well as in peritoneal metastases in ovarian cancer (16,20). Increased seprase expression has also been associated with a more aggressive disease state in colon cancer (21,22), in osteosarcoma (23), and with lymph node metastases in human colorectal (14), pancreatic (24), and gastric cancers (25).…”