title: Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy.
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.
authors.affiliation: Departments of Digestive and Pediatric Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City, Tokushima, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Yusue
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Mami
authors.initials: M
authors.lastname: Kanamoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Yu
authors.initials: Y
authors.lastname: Saito
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.forename: Daichi
authors.initials: D
authors.lastname: Ishikawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D017115:Catheter Ablation; D015815:Cell Adhesion Molecules / Q000235:genetics; D003131:Combined Modality Therapy; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C497442:HIF1A protein, human; D018960:Hyaluronan Receptors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger