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


METHODS
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.
Associate Professor, Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University, Kochi, Japan. tyamada@kochi-u.ac.jp
Tomohiro
T
Yamada
Moritoshi
M
Uchida
Kang
K
Kwang-Lee
Naoya
N
Kitamura
Tomohide
T
Yoshimura
Eri
E
Sasabe
Tetsuya
T
Yamamoto
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics; D005952:Glucose-6-Phosphatase / Q000096:biosynthesis / Q000235:genetics; D006593:Hexokinase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009060:Mouth Floor / Q000378:metabolism; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D018709:Statistics, Nonparametric; D014059:Tongue / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019788:Fluorodeoxyglucose F18; C472074:HK1 protein, human; D006593:Hexokinase; D005952:Glucose-6-Phosphatase; D005947:Glucose