Fibroblast activation protein (FAP) expression in the stroma of pancreatic and ampullary epithelial tumors

Determining whether pancreatic and ampullary neoplasms harbor invasive carcinoma is crucial for clinical management but can be challenging. Fibroblast activation protein (FAP) is a transmembrane serine protease that is upregulated in tumor-associated stroma. In this study, we aim to evaluate FAP expression by immunohistochemistry (IHC) in the stroma of pancreatic and ampullary neoplasms to assess its potential utility as a marker of invasion. A total of 42 patients with resection specimens of pancreatic intraductal neoplasms (n = 14), pancreatic ductal adenocarcinoma (PDAC) arising from intraductal neoplasms (n = 10), ampullary adenomatous neoplasms (n = 9), ampullary adenocarcinoma (n = 8), and chronic pancreatitis (n = 1) were included. FAP-stained sections were evaluated, and its expression was scored by two practicing pathologists independently with consensus. An immunoreactive score (IRS) was generated by multiplying stain percentage and intensity. FAP expression was significantly increased in the stroma of invasive adenocarcinomas compared to non-invasive precursor lesions (p < 0.05). FAP was positive (mildly or strongly) in 29% (4/14) of pancreatic intraductal neoplasms, 100% (10/10) of PDAC, 0% (0/9) of ampullary adenomatous neoplasms, and 100% (8/8) of ampullary adenocarcinomas. Two cases of intraductal papillary mucinous neoplasms (IPMNs) showed strong FAP expression in the stroma associated with erosion/denudation of epithelial lining and mucin extravasation. This study, although limited in size, suggests FAP as a potentially useful adjunct to morphology in diagnosing invasive adenocarcinoma in pancreas and ampulla. It is important to be aware that FAP is not a specific marker for desmoplastic stroma.