Overexpression of Glut1 in lymphoid follicles correlates with false-positive 18F-FDG PET results in lung cancer staging

The evaluation of mediastinal lymph node involvement in non-small cell lung carcinoma (NSCLC) is very important for the selection of surgical candidates. PET using F-18-FDG has remarkably improved mediastinal staging in NSCLC. However, false 18F-FDG PET results remain a problem. This study was undertaken to identify histologic and immunohistochemical differences between cases showing false and true results of mediastinal lymph node involvement assessed by 18F-FDG PET. Methods: Preoperative 18F-FDG PET examinations were performed on 62 patients with NSCLC, and mediastinal lymph node sampling was done at thoracotomy or mediastinoscopy. In 111 lymph nodes, the size, glucose transporter 1 (Glut1) expression, grade of follicular hyperplasia, and involved proportion of tumor were examined and compared with the 18F-FDG PET findings. Results: Lymphoid follicular cells were strongly positive for the expression of Glut1. The grade of follicular hyperplasia in false-positive lymph nodes was higher than that in true-negative nodes (P < 0.001). The Glut1 expression of metastatic tumors was higher in true-positive nodes than that in false-negative nodes (P < 0.001). Metastatic squamous cell carcinomas showed stronger Glut1 expression than adenocarcinomas and no false-negative results on 18F-FDG PET. On the other hand, metastatic adenocarcinomas exhibited focal and weak Glut1 expression with frequent false-negative results. Conclusion: The results of this study indicate that (a) lymphoid follicular hyperplasia with Glut1 overexpression may have a causal relationship with high 18F-FDG uptake of false-positive nodes and (b) the lower expression of Glut1 in metastatic tumors, such as adenocarcinomas, might be responsible for false-negative lymph nodes.