Fibroblast activation protein and its prognostic significance in correlation with vascular endothelial growth factor in pancreatic adenocarcinoma

Abstract

Fibroblast activation protein (FAP), a selective protein for tumor stromal fibroblasts, is expressed in >90% of human epithelial carcinomas. A characteristic feature of pancreatic cancer is an extensive fibrotic or desmoplastic reaction surrounding the primary tumor. The present study aimed to evaluate the expression levels of FAP and vascular endothelial growth factor (VEGF) and determine their correlation in pancreatic adenocarcinoma. Confocal laser scanning microscopy and conventional immunohistochemical analysis were used to quantify FAP and VEGF expression levels in formalin‑fixed and paraffin‑embedded tissue biopsies from 46patients (male,26; female,20; mean age, 66years; age range, 53‑80years) with pancreatic adenocarcinoma stageIIA orIIB. The expression levels of FAP in the neoplastic and adjacent normal tissue were significantly higher in stageIIB patients, compared with stageIIA patients. FAP expression was correlated with positive lymph nodes, resulting in poor prognosis for stageIIB patients. The partial correlation coefficient between FAP and VEGF expression levels was 0.39 (P=0.007), and the two factors had an effect on patient survival. Multivariate analysis demonstrated the prognostic superiority of FAP over VEGF, which is considered to be the most consistently reproducible molecular marker with prognostic value in resected pancreatic adenocarcinoma. Due to the limited beneficial effect of current systemic therapies for pancreatic adenocarcinoma, targeting FAP may be a potential therapeutic strategy and requires further investigation.