Correlation of positron emission tomography (PET)-avidity in esophageal and cardiac adenocarcinomas with hypoxia-related biomarkers

Abstract

4045 Background: PET is a non-invasive diagnostic tool in oncology that reflects tissue metabolism by a variable uptake of 18F-fluoro-deoxy-D-glucose (FDG). Glucose metabolism and neovascularization are activated by hypoxia. Hypoxic tumors have a poor prognosis and poor response to radiotherapy. We aimed at correlating the avidity of PET in esophageal and cardiac carcinomas with hypoxia-related markers: glut-1 and glut-3 (glucose transporters); vascular-endothelial growth factor (VEGF), a pro-angiogenic factor; carbonic anhydrase IX (CA IX), a marker for chronic hypoxia. Methods: Our retrospective study comprised 89 patients (65 yr, 32–83 yr, M/F=4.5) treated with primary surgery. Exclusion criteria were neo-adjuvant therapy and a tumor < 1 cm on ultrasound. PET before surgery was scored: PET1 = intense hot spot (n=47), PET2 = limited positivity (n=10), PET3 = inhomogeneous labeling (n=11), PET4 = no hot spot (n=21). Immunohistochemistry was performed on formol-fixed paraffin-embedded samples of resection specimens. Antibodies used: glut-1 (Chemicon, 1/1000), glut-3 (Chemicon, 1/500), CA IX (clone M75, 1/20), VEGF (SantaCruz, 1/100). The expression of these antibodies was evaluated semi-quantitatively. Statistical analysis: Chi2-test. Results: The overall prevalence of the antibodies was: glut-1 47%, glut-3 28%, VEGF 66% and CA IX 45%. The expression varied in function of the avidity in PET. Compared to non-avide tumors (PET4), PET1-tumors showed a significantly higher prevalence of glut-1-positivity (62 % vs. 24 %, p=0.009). These tumors also expressed more frequently VEGF (72% vs. 48%), CA IX (59% vs. 33%) and glut-3 (35% vs. 19%) than non-avide tumors. PET-positive tumors show a higher expression of glut-1 (p=0.01) and VEGF (p=0.003) than non-avide tumors. Conclusions: Our study shows that there is a relationship between the FDG avidity of a tumor on PET and different hypoxic markers. Avide tumors express more frequently these biomarkers. Hence PET may be used to select patients with a more hypoxic tumor, which is associated with a poor prognosis and a poor response to radiotherapy. No significant financial relationships to disclose.