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 (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 FDG-positron emission tomography (PET) scans were available, were included in this study (n = 108). 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 FDG-uptake, in general regarded as a poor prognostic factor, adenocarcinomas have a higher metastatic potential and a worse DFS. These findings show that FDG-PET should be interpreted in relation to histology. This may improve the prognostic potential of FDG-PET and may aid in exploiting FDG-PET in treatment strategies allied to histology.
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 (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 FDG-positron emission tomography (PET) scans were available, were included in this study (n = 108). 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 FDG-uptake, in general regarded as a poor prognostic factor, adenocarcinomas have a higher metastatic potential and a worse DFS. These findings show that FDG-PET should be interpreted in relation to histology. This may improve the prognostic potential of FDG-PET and may aid in exploiting FDG-PET in treatment strategies allied to histology.
Authors: Michael Messerli; Fotis Kotasidis; Irene A Burger; Daniela A Ferraro; Urs J Muehlematter; Corina Weyermann; David Kenkel; Gustav K von Schulthess; Philipp A Kaufmann; Martin W Huellner Journal: Br J Radiol Date: 2019-02-26 Impact factor: 3.039
Authors: Neil M Woody; Kevin L Stephans; Martin Andrews; Tingliang Zhuang; Priyanka Gopal; Ping Xia; Carol F Farver; Daniel P Raymond; Craig D Peacock; Joseph Cicenia; Chandana A Reddy; Gregory M M Videtic; Mohamed E Abazeed Journal: J Thorac Oncol Date: 2016-12-22 Impact factor: 15.609
Authors: Weiruo Zhang; Gina Bouchard; Alice Yu; Majid Shafiq; Mehran Jamali; Joseph B Shrager; Kelsey Ayers; Shaimaa Bakr; Andrew J Gentles; Maximilian Diehn; Andrew Quon; Robert B West; Viswam Nair; Matt van de Rijn; Sandy Napel; Sylvia K Plevritis Journal: Cancer Res Date: 2018-05-14 Impact factor: 12.701
Authors: Jia Wu; Todd Aguilera; David Shultz; Madhu Gudur; Daniel L Rubin; Billy W Loo; Maximilian Diehn; Ruijiang Li Journal: Radiology Date: 2016-04-05 Impact factor: 11.105