Increased Activity of Matrix Metalloproteinase 2 and 9 After Hepatic Radiofrequency Ablation

Abstract

Radiofrequency (RF) ablation of hepatic metastases from colorectal cancer (CRC) is associated with a high rate of local and intrahepatic tumor recurrence. Matrix metalloproteinases (MMPs) play an important role in inflammation, tissue repair and tumor cell invasion and metastasis. MMP-2 and MMP-9 are associated with increased risk of recurrence and decreased survival in patients with colorectal cancer. The primary aim of the study was to determine if hepatic RF ablation increased MMP-2 and MMP-9 activity in the transition zone surrounding the coagulated hepatic tissue. Twelve pigs were randomized to hepatic RF ablation with (n = 6) or without (n = 6) hepatic vascular occlusion (Pringle maneuver). Four days after ablation tissue specimens were collected from the transition zone surrounding coagulated hepatic tissue, and from normal hepatic parenchyma. MMP activity was quantified by gelatin zymography. Cellular localization of MMPs was determined by immunohistochemistry using antibodies against MMP-2, MMP-9, and the macrophage marker CD68. MMP-2 and MMP-9 activity was increased in the transition zone compared to normal hepatic parenchyma, with ratios of 3.0 (P = 0.005) and 2.6 (P = 0.001), respectively. Pringle maneuver did not influence MMP activity. MMP-2 and MMP-9 expression was localized to macrophages in the transition zone. Hepatic RF ablation is associated with increased expression of MMP-2 and MMP-9 in macrophages in the transition zone surrounding the coagulated hepatic parenchyma. These findings may contribute to the understanding of possible mechanisms for the high recurrence rates observed in patients after RF ablation of CRC hepatic metastases.