Norimitsu Kasahara1, Kyoichi Kaira2, Koichi Yamaguchi3, Hiroaki Masubuchi3, Hiroaki Tsurumaki3, Kenichiro Hara3, Yasuhiko Koga3, Reiko Sakurai4, Tetsuya Higuchi5, Tadashi Handa6, Tetsunari Oyama6, Takehiko Yokobori7, Kimihiro Shimizu8, Takayuki Asao1, Takeshi Hisada9. 1. Innovative Medical Research Center, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan. 2. Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Saitama 350-1298, Japan. Electronic address: kkaira1970@yahoo.co.jp. 3. Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. 4. Oncology Center, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan. 5. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. 6. Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. 7. Department of Innovative Cancer Immunotherapy, Gunma University 3-39-22 Showamachi, Maebashi 371-8511, Japan; Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR) 3-39-22 Showamachi, Maebashi 371-8511 Japan. 8. Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. 9. Graduate School of Health Sciences, Gunma University, Maebashi, Gunma 371-8514, Japan.
Abstract
OBJECTIVES: Positron emission tomography (PET) using 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) is a clinically useful modality for cancer evaluation. The mechanism of 18F-FDG uptake within cancer cells involves the glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1 α (HIF-1α). Although recent research has shown its clinical efficacy in small-cell lung cancer (SCLC), no suitable biomarker has been identified. We conducted a clinicopathological study to examine the relationship between tumor immunity and 18F-FDG uptake in patients with SCLC. MATERIALS AND METHODS: Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and 18F-FDG uptake was analyzed. Student's t-test, χ2 test, non-parametric Spearman's rank test, and Kaplan-Meier method were used to evaluate associations between the variables. RESULTS: A total of 98 patients 78 men and 20 women who underwent 18F-FDG PET, were enrolled in this study. PD-L1 was expressed in 36.7% (36/98) of all patients; this was significantly associated with GLUT1 expression (p = 0.04). The accumulation of 18F-FDG was significantly higher in patients with low CD8 and CD4 TILs than in those with high TILs (p = 0.03 and p = 0.01, respectively). The uptake of 18F-FDG was not significantly associated with the expression of either Foxp3 or PD-L1. Multivariate analysis demonstrated that advanced stage, poor ECOG-PS, and high SUVmax were independent predictors of poor OS. Among patients with limited-stage disease, multivariate analysis confirmed high PD-L1 expression and a high SUVmax to be independent predictors of poor OS. However, only ECOG-PS was found to be an independent predictor of poor OS among patients with extensive-stage tumors. CONCLUSION: High SUVmax on 18F-FDG-PET is correlated with low expression of CD8(+) and CD4(+) TILs, but is an independent prognostic factor for OS, particularly in those with limited disease. Further studies are warranted to validate our findings.
OBJECTIVES: Positron emission tomography (PET) using 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) is a clinically useful modality for cancer evaluation. The mechanism of 18F-FDG uptake within cancer cells involves the glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1 α (HIF-1α). Although recent research has shown its clinical efficacy in small-cell lung cancer (SCLC), no suitable biomarker has been identified. We conducted a clinicopathological study to examine the relationship between tumor immunity and 18F-FDG uptake in patients with SCLC. MATERIALS AND METHODS:Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and 18F-FDG uptake was analyzed. Student's t-test, χ2 test, non-parametric Spearman's rank test, and Kaplan-Meier method were used to evaluate associations between the variables. RESULTS: A total of 98 patients 78 men and 20 women who underwent 18F-FDG PET, were enrolled in this study. PD-L1 was expressed in 36.7% (36/98) of all patients; this was significantly associated with GLUT1 expression (p = 0.04). The accumulation of 18F-FDG was significantly higher in patients with low CD8 and CD4 TILs than in those with high TILs (p = 0.03 and p = 0.01, respectively). The uptake of 18F-FDG was not significantly associated with the expression of either Foxp3 or PD-L1. Multivariate analysis demonstrated that advanced stage, poor ECOG-PS, and high SUVmax were independent predictors of poor OS. Among patients with limited-stage disease, multivariate analysis confirmed high PD-L1 expression and a high SUVmax to be independent predictors of poor OS. However, only ECOG-PS was found to be an independent predictor of poor OS among patients with extensive-stage tumors. CONCLUSION: High SUVmax on 18F-FDG-PET is correlated with low expression of CD8(+) and CD4(+) TILs, but is an independent prognostic factor for OS, particularly in those with limited disease. Further studies are warranted to validate our findings.