Prognostic value of 2-[18F]-Fluoro-2-Deoxy-D-Glucose uptake on Positron Emission Tomography and biological markers in thymic epithelial tumors.

OBJECTIVE: 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) may predict the grade of malignancy and prognosis in thymic epithelial tumors. Biologic markers related to cell proliferation may be overexpressed in this setting and they are potentially correlated to 18F-FDG uptake. The aim of this study analyzed the correlation between the biologic markers and 18F-FDG uptake. METHODS: We reviewed the specimen of 49 patients with thymic epithelial tumors who underwent 18F-FDG PET. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), hypoxia-inducible factor-(HIF)-1alpha, vascular endothelial growth factor (VEGF), microvessels density (MVD) by CD31 and CD34, cell cycle control (p53, p21,p27) and apoptosis (bcl-2) markers. The expressions of all these markers were scored as low and high. Relationships between 18F-FDG PET standard uptake values and all these markers were studied by non-parametric tests. Survival studies were also conducted by Kaplan-Meier method and log rank test. RESULTS: There was a positive correlation between 18F-FDG uptake and GLUT1 (P=0.0017), HIF-1alpha (P=0.0036), VEGF (P=0.0009), MVD (P=0.0021), p53 (P=0.0002) p21 (P=0.0012) and p27 (P=0.0002), but not with bcl-2. High standardize value (>4.5) of 18F-FDG uptake (P=0.022), high expression of GLUT1 (P=0.016), HIF-1alpha (P=0.034), VEGF (P=0.026), MVD by CD31(P=0.043) and CD34 (P=0.031), and p53 (P=0.038) as well as low expression of p21 (P=0.011) and p27 (P=0.0023) were also significantly associated with shorter survival. CONCLUSION: Standardize values of 18F-FDG uptake in thymic epithelial tumors are correlated to glucose metabolism (GLUT1), hypoxia (HIF-1alpha), angiogenesis (VEGF, CD31 and CD34), and cell cycle regulator (p53,p21 and p27). All these variables were associated to the prognosis.