title: VEGFR-2 expression in HCC, dysplastic and regenerative liver nodules, and correlation with pre-biopsy Dynamic Contrast Enhanced CT.
abstract: OBJECTIVE
  To evaluate whether VEGFR-2-expression in hepatocellular carcinoma (HCC), dysplastic (DLN) and regenerative liver nodules (RLN) correlates with pre-histology, in vivo Dynamic Contrast Enhanced-Computed Tomography (DCE-CT) data as VEGFR-2-expression affects prognosis and therapeutic options.
  
  
  METHODS
  34 patients (63.6±8.9years, 7 females) underwent liver biopsy or surgery due to suspected HCC or dysplastic nodules after DCE-CT between 2009 and 2015 with no previous chemo- or interventional therapy. Immunohistochemistry staining for VEGFR-2 was performed using Immunoreactive-Remmele-Stegner-Score (IRS) for quantification. A 128-row CT-scanner was used for DCE-CT with assessment of perfusion parameters blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal venous perfusion (PVP), and hepatic perfusion index (HPI).
  
  
  RESULTS
  Histology confirmed HCC (n=10), DLN (n=7) and RLN (n=34). Mean IRS for VEGFR-2 in HCCs was 9.1±3.0, 7.3±1.6 for DLN and 5.2±2.8 for RLN (p=0.0004 for HCC vs. RLN). Perfusion values varied significantly between all three groups for BF and HPI (p<0.001 and p<0.0001) and for BV in HCC vs. RLN (p<0.0001) and DLN vs. RLN (p=0.0019). Strong correlations between VEGFR-2-IRS and perfusion parameters were observed for BF in HCC (r=0.88, p<0.01) and HPI in HCC and DLN (r=0.85, p<0.04; r=0.9, p<0.01).
  
  
  CONCLUSIONS
  Immunostaining revealed different VEGFR-2-expression levels in HCC, dysplastic and regenerative liver nodules. Perfusion markers blood flow, blood volume and hepatic perfusion index correlated well with VEGFR-2-immunostaining. This non-invasive discrimination between regenerative and dysplastic/HCC nodules might open new perspectives for diagnosis, therapy planning, and anti-VEGFR therapy monitoring.
authors: Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany(2). Electronic address: wolfgang.thaiss@med.uni-tuebingen.de.
authors: W M
authors: WM
authors: Thaiss
authors: Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany(2). Electronic address: sascha.kaufmann@med.uni-tuebingen.de.
authors: S
authors: S
authors: Kaufmann
authors: Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany(2). Electronic address: christopher.kloth@med.uni-tuebingen.de.
authors: C
authors: C
authors: Kloth
authors: Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany(2). Electronic address: konstantin.nikolaou@med.uni-tuebingen.de.
authors: K
authors: K
authors: Nikolaou
authors: Eberhard Karls University, Department of Pathology, Liebermeisterstraße 8, D-72076 Tuebingen, Germany. Electronic address: hans.boesmueller@med.uni-tuebingen.de.
authors: H
authors: H
authors: Bösmüller
authors: Eberhard Karls University, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany(2). Electronic address: Marius.Horger@med.uni-tuebingen.de.
authors: M
authors: M
authors: Horger
mesh_terms: D000368:Aged; D001706:Biopsy; D001810:Blood Volume; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D008875:Middle Aged; D055420:Perfusion Imaging; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D036542:Tomography, Spiral Computed / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: DCE-CT; HCC; Perfusion imaging; VEGFR-2