Heat Shock Protein 70 Expression Following Hepatic Radiofrequency Ablation is Affected by Adjacent Vasculature

Abstract

Heat shock proteins are a highly conserved family of stress response proteins. Members of the heat shock protein 70 (Hsp70) family prevent protein misfolding and aggregation. Following radiofrequency ablation of unresectable liver tumors an interface appears between the irreversibly damaged and normal liver. The fate of this transition zone is critical and is believed to be responsible for local recurrences. Hsp70 is expressed in response to thermal stress and may influence the fate of cells in this transitional zone. It is also recognized that the presence of large vessels or a perivascular location of tumors also influences the recurrence rate. The aim of this study is to examine the transition zone and observe the effect of local blood flow on ablation morphology and Hsp70 expression. Radiofrequency ablation was performed in 25 rats at various distances from the liver hilum. Tissue was retrieved and analysed at time points 0, 4, 24, 48 h, and 2 wk following treatment. Tissue was analyzed histologically with hematoxylin and eosin staining (H and E,) and immunohistochemically for Hsp70 expression. All rats survived the procedure. H and E staining revealed previously unreported foci of apoptosis at the ablation edge and deep in the normal hepatic parenchyma. Hsp70 was expressed in the transition zone at 4 h and peaked at 24 h. The degree of Hsp70 expression was significantly influenced by the distance from surrounding vasculature. This study reports several previously unreported findings. There is increased apoptosis distal to the ablated zone suggests leakage of radiofrequency (RF) current down blood vessels originating in the ablation zone. The degree of Hsp70 expression in the transition zone correlates with time after treatment and the size and location of any adjacent vasculature. These findings suggest that heat shock proteins may play a role in the ability of damaged cells to recover and survive at the periphery of an ablation zone.