03:09 PM Abstract No. 180 Liver radiofrequency ablation affects the infiltrated cellular dynamics in the periablational rim and induces aggressiveness in the distant subcutaneous R3230 breast adenocarcinoma tumor

Abstract

To assess the effect of normal non-tumor liver thermal ablation on periablation rim and distant R3230 breast adenocarcinoma tumor in F344 rats while using atorvastatin as an adjuvant tumor inhibitor. To this end, we used F344 rat (150g, n=65), R3230 breast adenocarcinoma tumor, sham (needle placement without energy for 5 minutes) or RFA (70°C for 5 minutes) with or without atorvastatin IP administration (1.15mg per rat) were used for this study. The rats were grouped into; sham, sham + 24 h post-ablation treatment, sham + daily (0, 24 and 48 h) post-ablation treatment, RFA only, RFA+24 h post-ablation treatment and RFA + daily (0, 24 and 48 h) post-ablation treatment. Tumors were measured daily post-R3230 transplantation until liver harvest at day 3 and 7 post-ablation for IHC and Elisa. We assessed the levels myofibroblast and macrophage infiltration (SMA and CD68 respectively), Ki-67 proliferative indexes, CD34 microvascular density and hepatic growth factor (HGF) in the harvested liver samples. From day 3 to day 7 post-ablation, RFA group significantly increased the distant tumor size when compared to the rest of the treatment groups. RFA + daily (0, 24 and 48 h) atorvastatin treatment group had the least distant tumor growth effect relative to the ablated groups. While there was no significant difference in the amount of SMA expressed in all the sham groups with or without atorvastatin, more than 2-fold increase in the levels of SMA, KI-67, CD38 and CD68 were observed in the periablational rim of the RFA group unlike RFA + 24 h atorvastatin treatment and RFA + daily (0, 24 and 48 h) atorvastatin treatment groups. Also, HGF was least expressed in RFA + daily (0, 24 and 48 h) atorvastatin treatment but not RFA group. RFA + 24 h atorvastatin treatment group showed a moderate level of HGF while there was generally no significant difference among the sham groups (with or without atorvastatin). Our results suggest that the ablation of normal non-tumor bearing liver affects distant subcutaneous R3230 breast tumor growth and alters the infiltrated cellular dynamics of the periablational rim when treated with or without atorvastatin after ablation.