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

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Glucose Metabolism in NSCLC Is Histology-Specific and Diverges the Prognostic Potential of 18FDG-PET for Adenocarcinoma and Squamous Cell Carcinoma  Olga C.J. Schuurbiers, MD, PhD, Tineke W.H. Meijer, MD, Johannes H.A.M Kaanders, MD, PhD, Monika G. Looijen-Salamon, MD, PhD, Lioe-Fee de Geus-Oei, MD, PhD, Miep A. van der Drift, MD, PhD, Erik H.F.M van der Heijden, MD, PhD, Wim J. Oyen, MD, PhD, Eric P. Visser, PhD, Paul N. Span, PhD, Johan Bussink, MD, PhD  Journal of Thoracic Oncology  Volume 9, Issue 10, Pages 1485-1493 (October 2014) DOI: 10.1097/JTO.0000000000000286 Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Flowchart of inclusion and exlusion criteria for correlation and follow-up analyses. Monocarboxylate transporter (MCT1) qPCR analysis failed in one tumor. NSCLC, non–small-cell lung carcinoma; FDG-PET, 18-fluoro-2-deoxyglucose positron emission tomography; qPCR, quantitative polymerase chain reaction. Journal of Thoracic Oncology 2014 9, 1485-1493DOI: (10.1097/JTO.0000000000000286) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Immunofluorescent images of squamous cell non–small-cell lung carcinomas showing GLUT1 (A), CAIX (B), MCT1 (C), and MCT4 (D) protein expression. GLUT1, CAIX, and MCT4 expressions show a diffusion-limited pattern, whereas MCT1 is up-regulated at the proximity of vessels. Red, GLUT1, CAIX, MCT1, or MCT4; green, vessels; magnification 100×; scale bars represent 100 μm. GLUT1, glucose transporter 1; MCT1, monocarboxylate transporter 1; CAIX, carbonic anhydrase IX; MCT4, monocarboxylate transporter 4. Journal of Thoracic Oncology 2014 9, 1485-1493DOI: (10.1097/JTO.0000000000000286) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Tumor microenvironment and tumor glucose metabolism of adeno- versus squamous cell carcinomas. A–D, Squamous cell carcinomas demonstrate higher expression of the hypoxia- and glycolysis-related markers on both protein and messenger ribonucleic acid (mRNA) level, with the exception of MCT4 compared with adenocarcinomas. E, Vascular density (number of vessels per squared millimeter) is significantly higher in adenocarcinomas. F–H, Squamous cell carcinomas are better visualized on 18-fluoro-2-deoxyglucose positron emission tomography as measured by TLG (mean standardized uptake value × metabolic tumor volume [cm3]) (F). G, Demonstrates a pT1aN0M0 adenocarcinoma with a tumor size of 2 cm. TLG is 8.6. H, Shows a pT2aN0M0 squamous cell carcinoma. Tumor size is 4.5 cm and TLG is 263.6. mRNA levels are expressed as ratios of hypoxanthine ribosyltransferase (HPRT). The Boxes represent lower quartile, median value and upper quartile, and whiskers represent minimum and maximum value. GLUT1, glucose transporter 1; CAIX, carbonic anhydrase IX; MCT1, monocarboxylate transporter 1; MCT4, monocarboxylate transporter 4; TLG, total lesion glycolysis. Journal of Thoracic Oncology 2014 9, 1485-1493DOI: (10.1097/JTO.0000000000000286) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Disease-free survival according to histological subtype (A) and TLG in adenocarcinomas (B). Cut-off value of TLG is set at median (11.1). TLG, total lesion glycolysis. Journal of Thoracic Oncology 2014 9, 1485-1493DOI: (10.1097/JTO.0000000000000286) Copyright © 2014 International Association for the Study of Lung Cancer Terms and Conditions