期刊
JOURNAL OF THORACIC ONCOLOGY
卷 9, 期 10, 页码 1485-1493出版社
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0000000000000286
关键词
Non-small-cell lung cancer; Hypoxia-related markers; 18-Fluoro-2-deoxyglucose positron emission tomography; Tumor microenvironment; Tumor glucose metabolism; Prognosis
资金
- METOXIA (Metastatic Tumors Facilitated by Hypoxic Tumor Micro-Environment
- EU 7th Research Framework Programme-Theme HEALTH) [222741]
Introduction: Biological features of non-small-cell lung carcinomas (NSCLCs) are important determinants for prognosis. In this study, differences in glucose metabolism between adeno-and squamous cell NSCLCs were quantified using the hypoxia and glycolysis-related markers glucose transporter 1 (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 (MCT1) and 4 (MCT4) vasculature, and 18-fluoro-2-deoxyglucose ((18)FDG)-uptake. Relevance of these markers for disease-free survival (DFS) was analyzed. Methods: Patients with curatively resected stage I to II and resectable stage IIIA, cN0-1 adeno-or squamous cell NSCLC, of whom fresh-frozen lung resection biopsies and pretreatment (18)FDG-positron emission tomography (PET) scans were available, were included in this study (n = 108). (18)FDG-uptake was quantified by calculating total lesion glycolysis (TLG). Metabolic marker expression was measured by immunofluorescent staining (protein) and quantitative polymerase chain reaction (messenger ribonucleic acid [mRNA]). Patients were retrospectively evaluated for DFS. Results: mRNA and protein expression of metabolic markers, with the exception of MCT4, and TLG were higher in squamous cell carcinomas than in adenocarcinomas, whereas adenocarcinomas were better vascularized. Adenocarcinomas had a worse DFS compared with squamous cell carcinomas (p = 0.016) based on the potential to metastasize. High TLG was associated with a worse DFS only in adenocarcinomas. Conclusion: Our findings suggest that the adenocarcinomas exhibit glycolysis under normoxic conditions, whereas squamous cell carcinomas are exposed to diffusion-limited hypoxia resulting in a very high anaerobic glycolytic rate. Although squamous cell carcinomas have a higher (18)FDG-uptake, in general regarded as a poor prognostic factor, adenocarcinomas have a higher metastatic potential and a worse DFS. These findings show that (18)FDG-PET should be interpreted in relation to histology. This may improve the prognostic potential of (18)FDG-PET and may aid in exploiting (18)FDG-PET in treatment strategies allied to histology.
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