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.
OBJECTIVE
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).


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.
Department of Human Oncology, University of Wisconsin, Madison, USA.
Andrew M
AM
Baschnagel
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
Jessica L
JL
Wobb
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
Joshua T
JT
Dilworth
Department of Pathology, William Beaumont Hospital, Royal Oak, USA.
Lindsay
L
Williams
Department of Pathology, William Beaumont Hospital, Royal Oak, USA.
Mohammad
M
Eskandari
Department of Nuclear Medicine, William Beaumont Hospital, Royal Oak, USA.
Dafang
D
Wu
Beaumont Biobank, William Beaumont Hospital, Royal Oak, USA.
Barbara L
BL
Pruetz
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA. Electronic address: George.Wilson@Beaumont.edu.
George D
GD
Wilson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C509805:KIF2A protein, human; C495677:SLC2A1 protein, human; D019788:Fluorodeoxyglucose F18; D066246:ErbB Receptors; D016547:Kinesins; D005947:Glucose
EGFR; FDG; GLUT1; HK2; HPV; p16