Evaluation of the Ki-67 labeling index on immediate pre-ablation biopsies as a predictive biomarker of local recurrence of colorectal cancer liver metastases

Abstract

The aim of this study was to evaluate if the Ki-67 labeling index (LI) on immediate pre-ablation biopsies of colorectal liver metastases (CLM) is associated with the presence of viable tumor cells in subsequent ablation zone biopsies and/or local tumor progression-free survival (LTPFS). Biopsies of CLM were performed before and after microwave ablation (MWA), as part of a prospective clinical trial between October 2013 and May 2019. Pre-ablation biopsy slides were examined for the Ki-67 LI using light microscopy. Ablation zone biopsy specimens were evaluated for the presence of viable tumor using hematoxylin-eosin and immunohistochemistry. Differences in CLM Ki-67 LI between positive and negative for viable tumor ablation zone biopsies were assessed using the Mann-Whitney U test. Biopsy, tumor and margin data were evaluated as predictors of LTPFS using Kaplan-Meier/Cox methods. Thirty-four patients with 48 CLM underwent biopsy before and after MWA. Sufficient tissue for Ki-67 labeling was obtained in 43/48 (89.6%) CLM. Viable tumor cells were detected in 11 ablation zones (22.9%). There was no significant difference in the CLM Ki-67 LI between the positive and negative for viable tumor ablation zones (mean: 69.2% vs. 64.3% respectively, p = 0.4). Adequate ablation zone margins (> 5 mm; p = 0.029) and negative ablation zone biopsies (p = 0.009) were significant predictors of longer LTPFS. KRAS status, tumor size and Ki-67 LI were not significant predictors of LTPFS. Complete tumor ablation (with adequate margins and negative ablation zone biopsies) is the most important factor in achieving local control of CLM, even for tumors exhibiting aggressive tumor biology.

Keywords: Biomarkers; Colorectal liver metastasis; Liver biopsy; Local tumor progression; Microwave ablation; Proliferation index.