Dynamic contrast-enhanced magnetic resonance imaging in cervical cancer: correlation between quantitative parameters and molecular markers hypoxia-inducible factors-1-alpha, vascular endothelial growth factor, and Ki-67

Clin Radiol. 2024 Jun;79(6):e826-e833. doi: 10.1016/j.crad.2024.01.039. Epub 2024 Mar 15.

Abstract

Aim: To investigate whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to non-invasively detect microenvironmental condition by quantitatively measuring blood perfusion, vessel wall permeability, and vascularity, and to elucidate the possible correlations between DCE-MRI quantitative parameters and the expression level of hypoxia, vascularity, and cell proliferation related molecular biomarkers.

Materials and methods: In this prospective single center clinical study, 58 patients diagnosed with cervical cancer underwent DCE-MRI before anticancer treatment were enrolled. Ktrans, Kep, Ve, and Vp were generated from Extended Toft's model. Then patients conducted colposcopy biopsy within 1 week after DCE-MRI. Pretreatment expression levels of HIF-1α, VEGF and Ki-67 were assessed and scored by immunohistochemistry on colposcopy obtained tumor specimens.

Results: In HIF-1α low-expression group, Ktrans (p=0.031) and Kep (p=0.012) values were significantly higher than the high-expression group. In VEGF high-expression group, Ktrans (p=0.044) and Ve values (p=0.021) were significantly higher than the low-expression group. In Ki-67 high-expression group, Ktrans (p=0.026) and Kep (p=0.033) were significantly higher than the low-expression group. Multiple linear regression analyses and Pearson correlation revealed that Ktrans independently negatively correlated with HIF-1α expression, Ve independently positively correlated with VEGF, and Kep independently positively correlated with Ki-67. The area under the ROC curves of Ktrans for HIF-1α, Ve for VEGF, and Kep for Ki-67 were 0.728, 0.743, 0.730, respectively.

Conclusion: Our results suggest that DCE-MRI quantitative parameters could be potentially used as imaging markers for non-invasively detecting microenvironmental hypoxia, vascularity and proliferation in cervical cancer patients.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / metabolism
  • Contrast Media*
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Ki-67 Antigen* / metabolism
  • Magnetic Resonance Imaging* / methods
  • Middle Aged
  • Prospective Studies
  • Uterine Cervical Neoplasms* / blood supply
  • Uterine Cervical Neoplasms* / diagnostic imaging
  • Uterine Cervical Neoplasms* / metabolism
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Ki-67 Antigen
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • Contrast Media
  • Biomarkers, Tumor
  • HIF1A protein, human