title: 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 46 patients (male, 26; female, 20; mean age, 66 years; age range, 53‑80 years) with pancreatic adenocarcinoma stage IIA or IIB. The expression levels of FAP in the neoplastic and adjacent normal tissue were significantly higher in stage IIB patients, compared with stage IIA patients. FAP expression was correlated with positive lymph nodes, resulting in poor prognosis for stage IIB 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.
authors.affiliation: Department of GI Surgery, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Patsouras
authors.affiliation: Gastroenterology Unit, 1st Department of Internal Medicine‑Propaedeutic, 'Laiko' General Hospital, Athens University Medical School, Athens GR‑11527, Greece.
authors.forename: Kostis
authors.initials: K
authors.lastname: Papaxoinis
authors.affiliation: Center of Experimental Surgery, Biomedical Research Foundation, Academy of Athens, Athens GR‑11527, Greece.
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Kostakis
authors.affiliation: Fourth Propedeutic Department of Surgery, Athens University Medical School, Attikon Hospital of Athens, Athens GR-12462, Greece.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Safioleas
authors.affiliation: 1st Department of Pathology, Athens University Medical School, Athens GR‑11527, Greece.
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Lazaris
authors.affiliation: 1st Department of Pathology, Athens University Medical School, Athens GR‑11527, Greece.
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Nicolopoulou-Stamati
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D010450:Endopeptidases; D005260:Female; D005455:Fluorescent Antibody Technique; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012697:Serine Endopeptidases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D042461:Vascular Endothelial Growth Factor A; D000099167:Fibroblast Activation Protein Alpha