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

• Published in: Journal of thoracic oncology 2014-10, Vol.9 (10), p.1485-1493
• Main Authors: Schuurbiers, Olga C.J., Meijer, Tineke W.H., Kaanders, Johannes H.A.M, Looijen-Salamon, Monika G., de Geus-Oei, Lioe-Fee, van der Drift, Miep A., van der Heijden, Erik H.F.M, Oyen, Wim J., Visser, Eric P., Span, Paul N., Bussink, Johan
• Format: Article
• Language: English
• Subjects: 18-Fluoro-2-deoxyglucose positron emission tomography; Adenocarcinoma - diagnostic imaging; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adenocarcinoma of Lung; Aged; Antigens, Neoplasm - metabolism; Carbonic Anhydrase IX; Carbonic Anhydrases - metabolism; Carcinoma, Squamous Cell - diagnostic imaging; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - surgery; Cell Hypoxia - physiology; Disease-Free Survival; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Glucose - metabolism; Glucose Transporter Type 1 - metabolism; Humans; Hypoxia-related markers; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Middle Aged; Monocarboxylic Acid Transporters - metabolism; Muscle Proteins - metabolism; Neoplasm Staging; Non–small-cell lung cancer; Positron-Emission Tomography - methods; Prognosis; Radiopharmaceuticals - pharmacokinetics; Symporters - metabolism; Tumor glucose metabolism; Tumor Microenvironment
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0000000000000286

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. 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. 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. 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.