Oncogenesis: An "off-target" effect of radiofrequency ablation

Nir Rozenblum, Evelyne Zeira, Viviana Scaiewicz, Baruch Bulvik, Svetlana Gourevitch, Hagit Yotvat, Eithan Galun, S. Nahum Goldberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Purpose: To compare hepatocellular carcinoma (HCC) development after radiofrequency (RF) ablation, partial surgical hepatectomy, and a sham operation and to inhibit HCC recurrence after RF ablation in a mouse model of spontaneously forming HCC in the setting of chronic inflammation (ie, the MDR2 knockout model). Materials and Methods: Animal experiments were performed according to an approved animal care committee protocol. The authors compared the survival of MDR2 knockout mice (an inflammation-induced HCC model) that underwent RF ablation, 35% partial hepatectomy (ie, left lobectomy), or a sham operation (controls) by using Kaplan-Meier survival curve analysis. Tumor load and tumor frequency in mice that underwent sham operation were further compared with those of mice treated with RF ablation at 1 month after therapy by using a two-tailed Student t test. Liver slices from mice treated with RF ablation were stained for α-smooth muscle actin and Ki-67 to establish the role of liver regeneration in the tumorigenic effect of RF ablation. Finally, tumor load and tumor incidence were evaluated in mice treated with a c-met inhibitor after RF ablation by using the Mann-Whitney U test. Results: Ablation of 3.5% ± 0.02 of the MDR2 knockout mice liver induced increased tumor load (P = .007) and reduced survival (P = .03) in comparison to that of controls, with no significant difference to the 10-fold volume removal of partial hepatectomy. Seven days after RF treatment, the border zone of the coagulation zone was surrounded by a2smooth muscle actin-positive activated myofibroblasts. A significant elevation of hepatocyte proliferation was also seen 7 days after RF ablation in the distant liver (ablated lobe: P = .003; untreated lobe: P = .02). A c-met inhibitor significantly attenuated HCC development in MDR2 knockout mice treated with RF ablation (P = .001). Conclusion: Liver regeneration induced by RF ablation facilitates c-met/hepatocyte growth factor axis-dependent HCC tumor formation after treatment in the MDR2 knockout model. Blockage of the c-met/hepatocyte growth factor axis attenuates HCC recurrence, raising the potential for therapeutic intervention to reverse this potentially deleterious tumorigenic effect.

Original languageAmerican English
Pages (from-to)426-432
Number of pages7
JournalRadiology
Volume276
Issue number2
DOIs
StatePublished - 1 Aug 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© RSNA, 2015.

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