title: 18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1α, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours.
abstract: OBJECTIVE
  The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours.
  
  
  METHODS
  Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1α, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales.
  
  
  RESULTS
  FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1α, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1α showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1α and Glut-1, and HIF-1α and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1α and Glut-1 were partly expressed in non-neoplastic immature lymphocytes.
  
  
  CONCLUSIONS
  FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1α, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.
authors.affiliation: Department of Thoracic and Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. toba1109@gmail.com
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toba
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kondo
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sadohara
authors.forename: Hideki
authors.initials: H
authors.lastname: Otsuka
authors.forename: Masami
authors.initials: M
authors.lastname: Morimoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kajiura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yukikiyo
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takizawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kenzaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Sakiyama
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.forename: Akira
authors.initials: A
authors.lastname: Tangoku
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D012372:ROC Curve; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018709:Statistics, Nonparametric; D013953:Thymus Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019275:Radiopharmaceuticals; C495677:SLC2A1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18
keywords: FDG-PET/CT; Glut-1; HIF-1α; SUVmax; Thymic epithelial tumour; VEGF; WHO classification