Glucose metabolism in NSCLC is histology-specific and diverges the prognostic potential of 18FDG-PET for adenocarcinoma and squamous cell carcinoma

J Thorac Oncol. 2014 Oct;9(10):1485-93. doi: 10.1097/JTO.0000000000000286.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • 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
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / pharmacokinetics
  • Symporters / metabolism
  • Tumor Microenvironment


  • Antigens, Neoplasm
  • Glucose Transporter Type 1
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • Radiopharmaceuticals
  • SLC16A4 protein, human
  • SLC2A1 protein, human
  • Symporters
  • monocarboxylate transport protein 1
  • Fluorodeoxyglucose F18
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • Glucose