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Facing the enigma of the vascular network in hepatocellular carcinomas in cirrhotic and non-cirrhotic livers
  1. Francesco Vasuri1,
  2. Silvia Fittipaldi1,2,
  3. Francesca Giunchi1,
  4. Melissa Monica1,
  5. Matteo Ravaioli3,
  6. Alessio Degiovanni1,
  7. Sonia Bonora1,
  8. Rita Golfieri4,
  9. Luigi Bolondi5,
  10. Walter F Grigioni1,
  11. Gianandrea Pasquinelli2,
  12. Antonia D'Errico-Grigioni1
  1. 1Department of Specialty, Diagnostic and Experimental Medicine (DIMES), “F. Addarii” Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy
  2. 2Department of Specialty, Diagnostic and Experimental Medicine (DIMES), Clinical Pathology, S. Orsola-Malpighi University Hospital, Bologna, Italy
  3. 3Department of General Surgery and Transplantation, S. Orsola-Malpighi University Hospital, Bologna, Italy
  4. 4Diagnostic and Interventional Radiology Unit, Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
  5. 5Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi University Hospital, Bologna, Italy
  1. Correspondence to Professor Antonia D'Errico-Grigioni, “F. Addarii” Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi University Hospital, V.le Ercolani 4/2, Bologna 40138, Italy; derrico{at}aosp.bo.it

Abstract

Aims 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.

  • LIVER CANCER
  • HISTOPATHOLOGY
  • ANGIOGENESIS
  • PCR
  • IMMUNOHISTOCHEMISTRY

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