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

Patsouras,Dimitrios; Papaxoinis,Kostis; Kostakis,Alkiviadis; Safioleas,Michael  C.; Lazaris,Andreas  C.; Nicolopoulou‑Stamati,Polyxeni

doi:10.3892/mmr.2015.3259

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

Authors:
- Dimitrios Patsouras
- Kostis Papaxoinis
- Alkiviadis Kostakis
- Michael C. Safioleas
- Andreas C. Lazaris
- Polyxeni Nicolopoulou‑Stamati
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Affiliations: Department of GI Surgery, St. Thomas' Hospital, London SE1 7EH, United Kingdom, Gastroenterology Unit, 1st Department of Internal Medicine‑Propaedeutic, ‘Laiko’ General Hospital, Athens University Medical School, Athens GR‑11527, Greece, Center of Experimental Surgery, Biomedical Research Foundation, Academy of Athens, Athens GR‑11527, Greece, Fourth Propedeutic Department of Surgery, Athens University Medical School, Attikon Hospital of Athens, Athens GR-12462, Greece, 1st Department of Pathology, Athens University Medical School, Athens GR‑11527, Greece
Published online on: January 27, 2015 https://doi.org/10.3892/mmr.2015.3259
Pages: 4585-4590

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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.

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