Correlation of metabolism/hypoxia markers and fluorodeoxyglucose uptake in oral squamous cell carcinomas

Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Apr;113(4):464-71. doi: 10.1016/j.tripleo.2011.04.006. Epub 2011 Jul 20.

Abstract

Objective: The objective of this study was to analyze the relationship between the uptake of (18)F-2-fluoro-2-deoxy-d-glucose (FDG) by positron emission tomography-computerized tomography (PET-CT) and glucose metabolism/hypoxia markers in oral squamous cell carcinoma (OSCC).

Study design: Thirty-six patients with OSCC (tongue [n = 23], buccal mucosa [n = 7], and floor of the mouth [n = 6]) were assessed and underwent incisional biopsy and subsequently received FDG-PET-CT. Expressions of hypoxia-inducible factor 1α (HIF-1α), glucose transporter protein 1 (GLUT-1), hexokinase-II (HK-II), and glucose-6-phosphatase (G6Pase) were immunohistochemically quantified, and FDG uptake was evaluated by the maximum standardized uptake values (SUV(max)) at the primary tumor site.

Results: FDG uptake was found to be significantly correlated with the T classification of OSCC but not with other clinicopathologic characteristics, such as the N classification, clinical type, and histologic grade of malignancy. In the early-stage (T1 and T2) tumor, FDG uptake was significantly associated with the expression levels of GLUT-1, HK II, and HIF-1α, and the expression levels of GLUT-1 and HK-II significantly correlated with HIF-1α expression levels. However, there were no correlations between the expression levels of these molecules and SUV(max) in the late-stage (T3 and T4) tumor.

Conclusions: FDG uptake was significantly associated with the expression levels of glucose metabolism-related molecules, such as GLUT-1, HK II, and HIF-1α, especially in early-stage tumors.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Fluorodeoxyglucose F18
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / biosynthesis
  • Glucose Transporter Type 1 / genetics
  • Glucose-6-Phosphatase / biosynthesis
  • Glucose-6-Phosphatase / genetics
  • Hexokinase / biosynthesis
  • Hexokinase / genetics
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Male
  • Middle Aged
  • Mouth Floor / metabolism
  • Mouth Mucosa / metabolism
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Neoplasm Grading
  • Neoplasm Staging
  • Positron-Emission Tomography
  • Statistics, Nonparametric
  • Tongue / metabolism

Substances

  • Glucose Transporter Type 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Fluorodeoxyglucose F18
  • HK1 protein, human
  • Hexokinase
  • Glucose-6-Phosphatase
  • Glucose