Norimitsu Kasahara1, Kyoichi Kaira2, Pinjie Bao3, Tetsuya Higuchi4, Yukiko Arisaka4, Bilguun Erkhem-Ochir5, Noriaki Sunaga6, Yoichi Ohtaki3, Toshiki Yajima3, Takayuki Kosaka3, Tetsunari Oyama7, Takehiko Yokobori8, Takayuki Asao9, Masahiko Nishiyama10, Yoshito Tsushima4, Hiroyuki Kuwano3, Kimihiro Shimizu3, Akira Mogi3. 1. Department of Respiratory Medicine, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan. 2. Department of Oncology Clinical Development, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan. Electronic address: kkaira1970@yahoo.co.jp. 3. Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan. 4. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan. 5. Department of Oncology Clinical Development, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan; Department of Molecular Pharmacology and Oncology, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan. 6. Oncology Center, Gunma University Hospital, Gunma 371-8511, Japan. 7. Department of Diagnostic Pathology, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan. 8. Division of Integrated Oncology Research, Research Program for Omics-based Medical Science, Gunma University Initiative for Advanced Research, Gunma 371-8511, Japan. 9. Big Data Center for Integrative Analysis, Gunma University Initiative for Advanced Research, Gunma 371-8511, Japan. 10. Department of Molecular Pharmacology and Oncology, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan.
Abstract
OBJECTIVES: 2-Deoxy-2-[fluorine-18] fluoro-d-glucose with positron emission tomography (18F-FDG-PET) is a clinically useful tool for cancer evaluation. 18F-FDG accumulation in tumor cells is known to be correlated with the presence of glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1α (HIF-1α). Although anti-programmed death-1 (PD-1) antibody treatments have been approved, no suitable predictor of significant responders has been identified. Based on the existing information, we investigated the relationship between tumor immunity (including PD-L1) and 18F-FDG uptake in patients with surgically resected pulmonary squamous-cell carcinoma (SQC). MATERIALS AND METHODS: This study included 167 patients (153 men and 14 women) with SQC who underwent 18F-FDG PET. 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, the χ2 test, non-parametric Spearman's rank test and the Kaplan-Meier method were used to show associations between variables. RESULTS: The rate of positive PD-L1 expression was 79% (132/167), and PD-L1 expression was significantly associated with GLUT1 (P < 0.01), HIF-1α (P < 10-4), and CD8 (P < 1 × 10-3) expression. The SUVmax of 18F-FDG was significantly correlated with PD-L1 (P = 0.02) and GLUT1 (P < 0.01) expression. Multivariate analysis demonstrated that advanced stage, elevated PD-L1 expression, and elevated SUVmax were independent prognostic factors for predicting poor OS. Among patients with a high SUVmax, multivariate analysis confirmed that advanced stage and high PD-L1 expression were independent prognostic factors for poor OS; however, there was no significant difference among patients with a low SUVmax. CONCLUSION: High SUVmax on 18F-FDG-PET is associated with PD-L1 expression but is an independent prognostic factor for OS in our population of surgically resected pulmonary squamous-cell carcinoma.
OBJECTIVES:2-Deoxy-2-[fluorine-18] fluoro-d-glucose with positron emission tomography (18F-FDG-PET) is a clinically useful tool for cancer evaluation. 18F-FDG accumulation in tumor cells is known to be correlated with the presence of glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1α (HIF-1α). Although anti-programmed death-1 (PD-1) antibody treatments have been approved, no suitable predictor of significant responders has been identified. Based on the existing information, we investigated the relationship between tumor immunity (including PD-L1) and 18F-FDG uptake in patients with surgically resected pulmonary squamous-cell carcinoma (SQC). MATERIALS AND METHODS: This study included 167 patients (153 men and 14 women) with SQC who underwent 18F-FDG PET. 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, the χ2 test, non-parametric Spearman's rank test and the Kaplan-Meier method were used to show associations between variables. RESULTS: The rate of positive PD-L1 expression was 79% (132/167), and PD-L1 expression was significantly associated with GLUT1 (P < 0.01), HIF-1α (P < 10-4), and CD8 (P < 1 × 10-3) expression. The SUVmax of 18F-FDG was significantly correlated with PD-L1 (P = 0.02) and GLUT1 (P < 0.01) expression. Multivariate analysis demonstrated that advanced stage, elevated PD-L1 expression, and elevated SUVmax were independent prognostic factors for predicting poor OS. Among patients with a high SUVmax, multivariate analysis confirmed that advanced stage and high PD-L1 expression were independent prognostic factors for poor OS; however, there was no significant difference among patients with a low SUVmax. CONCLUSION: High SUVmax on 18F-FDG-PET is associated with PD-L1 expression but is an independent prognostic factor for OS in our population of surgically resected pulmonary squamous-cell carcinoma.
Authors: Olivia R Stephens; Kelly Weiss; Matthew Frimel; Jonathan A Rose; Yu Sun; Kewal Asosingh; Samar Farha; Kristin B Highland; Sathyamangla V Naga Prasad; Serpil C Erzurum Journal: Am J Physiol Lung Cell Mol Physiol Date: 2019-06-26 Impact factor: 5.464