Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy

Ann Surg Oncol. 2014 Jun:21 Suppl 3:S436-42. doi: 10.1245/s10434-014-3575-z. Epub 2014 Feb 25.

Abstract

Background: Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive local recurrence of HCC after RFA, suggesting that induction of further malignant transformation of HCC has occurred.

Methods: Eighty-eight (88) patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and the patient's prognosis after hepatectomy were compared between the two groups. Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA (mRNA) in the tumor tissues were also examined.

Results: The RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05).

Conclusions: These results suggest that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC tumors after insufficient or sub-lethal treatment by RFA.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Case-Control Studies
  • Catheter Ablation*
  • Cell Adhesion Molecules / genetics
  • Combined Modality Therapy
  • Epithelial Cell Adhesion Molecule
  • Female
  • Follow-Up Studies
  • Hepatectomy
  • Humans
  • Hyaluronan Receptors / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Male
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Neoplasm, Residual / diagnosis
  • Neoplasm, Residual / mortality
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CD44 protein, human
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • HIF1A protein, human
  • Hyaluronan Receptors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger