title: Facing the enigma of the vascular network in hepatocellular carcinomas in cirrhotic and non-cirrhotic livers.
abstract: OBJECTIVE
  In this paper we aimed to analyse the typology and the phenotype of the different vascular modifications in human hepatocellular carcinomas (HCCs) with a new immunomorphological and gene expression approach. We also attempted to correlate these modifications with the histological parameters of tumour aggressiveness and the surrounding liver parenchyma.
  
  
  METHODS
  Ninety-six HCCs (from 80 patients) were retrospectively enrolled, 46 occurring in non-cirrhotic livers, and 50 in livers transplanted for cirrhosis. Histopathological analysis, immunohistochemistry for CD34, Nestin and WT1 and RT-PCR for Nestin, transforming growth factor-β1 (TGFβ1) and insulin-like growth factor 1 (IGF1R) mRNA were performed in all nodules.
  
  
  RESULTS
  By correlating the CD34 and Nestin immunoreactivity in HCC vasculature with the tumorous architecture, we identified four vascular patterns (named from 'a' to 'd'). Each of them was characterised by different expressions of TGFβ1 and IGF1R mRNA. Pattern a showed CD34-positive/Nestin-negative sinusoids, and was prevalent in microtrabecular lesions. Pattern b showed similar morphology and architecture as pattern a, but with Nestin-positive sinusoids and a significant 'boost' in IGF1R and TGFβ1 mRNAs. In patterns c and d a progressive sinusoid loss and a gain of newly formed arterioles were seen. Notably, HCCs with pattern a arose more frequently in cirrhosis (p=0.024), and showed lower incidence of microvascular invasion (p=0.002) and infiltration (p=0.005) compared with HCCs with other patterns.
  
  
  CONCLUSIONS
  Although future studies are surely required, the identification of different vascular profiles in HCCs from cirrhotic and non-cirrhotic livers may help clarify the relationship between HCC progression and aggressiveness.
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vasuri
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy Department of Specialty, Diagnostic and Experimental Medicine (DIMES), Clinical Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fittipaldi
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giunchi
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Monica
authors.affiliation: Department of General Surgery and Transplantation, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ravaioli
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Degiovanni
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bonora
authors.affiliation: Diagnostic and Interventional Radiology Unit, Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Golfieri
authors.affiliation: Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Walter F
authors.initials: WF
authors.lastname: Grigioni
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), Clinical Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Gianandrea
authors.initials: G
authors.lastname: Pasquinelli
authors.affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES), "F. Addarii" Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Errico-Grigioni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D064231:Nestin / Q000032:analysis / Q000235:genetics; D010641:Phenotype; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D025721:WT1 Proteins / Q000032:analysis; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C000597236:IGF1R protein, human; C577484:NES protein, human; D064231:Nestin; D017451:Receptors, Somatomedin; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D025721:WT1 Proteins; C583751:WT1 protein, human; D017526:Receptor, IGF Type 1
keywords: ANGIOGENESIS; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; LIVER CANCER; PCR