Incomplete thermal ablation stimulates proliferation of residual renal carcinoma cells in a translational murine model

Authors


Judith Jans, Department of Urology, University Medical Center Utrecht, Stratenum, STR02.118, Postbox 80030, 3508 TA Utrecht, the Netherlands. e-mail: j.j.m.jans@umcutrecht.nl

Abstract

What's known on the subject? and What does the study add?

Thermal ablation influences the local tissue microenvironment. Several studies have reported that residual tumour cells may exhibit a more aggressive phenotype.

This study shows that incomplete CA and RFA cause an increased proliferation and decreased apptosis of residual renal tumour cells. This may be caused by stimulatory factors such as hypoxia, HSPs and inflammatory cells.

OBJECTIVE

  • • To compare the effect of incomplete thermal ablation vs partial nephrectomy (PN) on growth stimulation and cellular survival in renal tumours.

MATERIALS AND METHODS

  • • Renca renal tumours were transplanted under the renal capsule of mice (four to six mice/group) after which incomplete radiofrequency ablation (RFA), cryoablation (CA) or PN was performed.
  • • At several time points after treatment, presence of cell proliferation, apoptosis, hypoxic areas, inflammatory factors and the heat-shock proteins (HSPs) 70 and 90 were evaluated using immunohistochemistry.

RESULTS

  • • At 2 h after thermal ablation residual tumour cells showed increased proliferation. This hyperproliferation was significantly stronger after RFA than CA (P < 0.05) and not present after PN.
  • • Residual cells showed increased apoptosis after 2 h and decreased apoptosis from 2 days after thermal ablation. Apoptotic cells were significantly less evident at 3 days after RFA (P < 0.001).
  • • Hypoxic areas and HSPs were increasingly present from 2 h up to 7 days after thermal ablation (P < 0.001).
  • • Inflammatory cells infiltrated mainly the necrotic areas after thermal ablation, and their abundance peaked at 1 week after ablation (P < 0.05).
  • • The increased cell growth was preceded by hypoxia and presence of HSPs.

CONCLUSIONS

  • • CA and RFA result in an increased proliferation and decreased apoptosis of residual renal tumour cells.
  • • This hyperproliferation may be caused by stimulatory factors, e.g. hypoxia, HSPs and inflammatory cells, and could facilitate recurrences of renal tumours after thermal ablation.
  • • This study highlights the importance of achieving complete tumour destruction.

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