Influence of tumor and microenvironment characteristics on diffusion-weighted imaging in oropharyngeal carcinoma: A pilot study

Oral Oncol. 2018 Feb:77:9-15. doi: 10.1016/j.oraloncology.2017.12.001. Epub 2017 Dec 12.

Abstract

Objectives: Diffusion weighted imaging (DWI) is a frequently performed MRI sequence in cancer patients. While previous studies have shown the clinical value of the apparent diffusion coefficient (ADC) for response prediction and response monitoring, less is known about the biological background of ADC. In the tumor microenvironment, hypoxia and increased proliferation of tumor cells contribute to resistance to (radio-)therapy, while high T-cell influx is related to better prognosis. We investigated the correlation between these three tissue characteristics and ADC in 20 oropharyngeal squamous cell carcinoma patients.

Materials and methods: 20 patients with oropharyngeal squamous cell carcinoma (OPSCC) who underwent 1.5 T MRI, including DWI were included in this pilot study. Corresponding formalin-fixed paraffin-embedded tumor tissues were immunohistochemically analyzed for protein expression of hypoxia-inducible factor 1a (HIF-1a), Ki-67 and CD3. Expression of these markers was correlated with ADC.

Results: ADC negatively correlated with Ki-67 expression (p = .024) in tumor cells. There was a significant negative correlation between ADC and CD3-positive cell count (p = .009). No correlation was observed between HIF-1a expression and ADC.

Conclusion: This study suggests that ADC reflects characteristics of tumor cells as well as the surrounding microenvironment. Interestingly, high tumor proliferation (a negative prognostic factor) and high T-cell influx (a beneficial prognostic factor) are both associated with a lower ADC. Further studies should be performed to correlate ADC to these histological characteristics in relation to previously known factors that affect ADC, to gain further knowledge on the role of DW-MRI in diagnostics and personalized medicine.

Keywords: Diffusion magnetic resonance imaging; Oropharyngeal neoplasms; Tumor microenvironment.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism
  • CD3 Complex / metabolism
  • Cell Hypoxia
  • Diffusion Magnetic Resonance Imaging / methods*
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ki-67 Antigen / metabolism
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / diagnostic imaging*
  • Oropharyngeal Neoplasms / metabolism
  • Oropharyngeal Neoplasms / pathology
  • Pilot Projects
  • Squamous Cell Carcinoma of Head and Neck / diagnostic imaging*
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Tumor Microenvironment*

Substances

  • Biomarkers, Tumor
  • CD3 Complex
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ki-67 Antigen