The association of (18)F-FDG PET and glucose metabolism biomarkers GLUT1 and HK2 in p16 positive and negative head and neck squamous cell carcinomas

Radiother Oncol. 2015 Oct;117(1):118-24. doi: 10.1016/j.radonc.2015.08.025. Epub 2015 Aug 29.

Abstract

Objectives: To investigate the relationship between FDG-PET maximum standard uptake value (SUVmax), p16, EGFR, GLUT1 and HK2 expression in head and neck squamous cell carcinomas (HNSCC).

Materials and methods: Immunohistochemical staining of p16, EGFR, GLUT1 and HK2 was performed on primary tumor tissue from 97 locally advanced HNSCC patients treated with definitive chemoradiation. SUVmax along with p16, EGFR, GLUT1 and HK2 expression were analyzed for associations including local control, locoregional control and disease free survival.

Results: Pretreatment SUVmax in primary tumors did not differ when stratified by p16, EGFR or GLUT1 expression but SUVmax was significantly higher in HK2 expressing tumors (p=0.021) and in tumors with higher T-stage (p=0.022). GLUT1 expression was significantly higher in p16 negative (p<0.001) and EGFR positive tumors (p<0.01). HK2 expressing tumors were associated with EGFR positive tumors (p=0.022) but not with p16 or GLUT1 expression. EGFR positive, p16 negative and high GLUT1 expressing tumors were associated with worse local control and disease free survival on univariate analyses. After adjusting for patient and treatment characteristics p16 status was the only factor that predicted for outcome on multivariate analysis.

Conclusions: High GLUT1 expression was associated with EGFR positive and p16 negative HNSCC tumors. GLUT1 maybe an important biomarker in HNSCC but its expression appears dependent on p16 status.

Keywords: EGFR; FDG; GLUT1; HK2; HPV; p16.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology
  • Chemoradiotherapy
  • Disease-Free Survival
  • ErbB Receptors / metabolism
  • Female
  • Fluorodeoxyglucose F18
  • Glucose / metabolism
  • Glucose Transporter Type 1 / metabolism*
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / therapy
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Kinesins / metabolism*
  • Male
  • Middle Aged
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / metabolism*
  • Positron-Emission Tomography / methods
  • Prognosis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • KIF2A protein, human
  • SLC2A1 protein, human
  • Fluorodeoxyglucose F18
  • ErbB Receptors
  • Kinesins
  • Glucose