Elsevier

Journal of Thoracic Oncology

Volume 9, Issue 10, October 2014, Pages 1485-1493
Journal of Thoracic Oncology

Original Articles
Glucose Metabolism in NSCLC Is Histology-Specific and Diverges the Prognostic Potential of 18FDG-PET for Adenocarcinoma and Squamous Cell Carcinoma

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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 (18FDG)-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 18FDG-positron emission tomography (PET) scans were available, were included in this study (n = 108). 18FDG-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 18FDG-uptake, in general regarded as a poor prognostic factor, adenocarcinomas have a higher metastatic potential and a worse DFS. These findings show that 18FDG-PET should be interpreted in relation to histology. This may improve the prognostic potential of 18FDG-PET and may aid in exploiting 18FDG-PET in treatment strategies allied to histology.

Key Words

Non–small-cell lung cancer
Hypoxia-related markers
18-Fluoro-2-deoxyglucose positron emission tomography
Tumor microenvironment
Tumor glucose metabolism
Prognosis

Cited by (0)

The first two authors contributed equally to this work.

Disclosure: The authors declare no conflict of interest.