Correlations between ADC values and molecular markers of Ki-67 and HIF-1α in hepatocellular carcinoma

Eur J Radiol. 2015 Dec;84(12):2464-9. doi: 10.1016/j.ejrad.2015.09.013. Epub 2015 Sep 21.

Abstract

Objective: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths. Cell proliferativity and hypoxia have important impact on the response to radiotherapy or chemotherapy. The purpose of this study was to investigate the association of apparent diffusion coefficient (ADC) values and the molecular markers Ki-67 and hypoxia inducible factor-α (HIF-α) in hepatocellular carcinoma (HCC).

Materials and methods: Forty-seven patients diagnosed with HCC were included in this study. All patients performed diffusion-weighted magnetic resonance imaging (DW-MRI) before any anticancer treatment. The ADC maps were automatically calculated on a Syngo workstation. The Ki-67 and HIF-1α expression were assessed by immunohistochemistry. The Pearson correlation test was used to assess the correlation between ADC values and Ki-67 and HIF-1α expression.

Results: Ki-67 staining was clearly identified based on the brown nuclear staining in tumor cells. High Ki-67 expression was correlated with low differentiation (p=0.028). A significant correlation was observed between HIF-1α expression and maximum diameter (p=0.014). The mean ADC value was (0.983±0.21)×10(-3) mm(2)/s. The level of Ki-67 expression was correlated inversely with the ADC values (r=-0.371, p=0.01). There was a significant positive correlation between the ADC values and HIF-1α expression (r=0.389, p=0.007).

Conclusion: The ADC values were observed to correlate significantly with the molecular markers Ki-67 and HIF-1α. Our results suggest that the ADC values on DW-MRI may be used as a measure of cell proliferativity and hypoxia in hepatocellular carcinoma.

Keywords: Apparent diffusion coefficient (ADC); Diffusion-weighted magnetic resonance imaging (DW-MRI); HIF-1α; Hepatocellular carcinoma; Ki-67.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Proliferation / genetics
  • Diffusion Magnetic Resonance Imaging / methods
  • Female
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ki-67 Antigen