18F-FDG Uptake in Well-Differentiated Neuroendocrine Tumors Correlates with Both Ki-67 and VHL Pathway Inactivation

Neuroendocrinology. 2018;106(3):274-282. doi: 10.1159/000480239. Epub 2017 Aug 11.

Abstract

Background: 18F-FDG-PET scan positivity correlates with poor prognosis in neuroendocrine neoplasms (NEN). Glucose transporter 1 (GLUT1) and carbonic anhydrase 9 (CA9) are markers of aggressiveness in tumors. Together with von Hippel-Lindau protein (pVHL), they are involved in tumor cell metabolism via the hypoxia-inducible factor signaling pathway. The aim of this study was to compare, in a series of well-differentiated neuroendocrine tumors (NET), the 18F-FDG uptake and expression of the proliferation markers Ki-67, GLUT1, CA9, and pVHL.

Patients and methods: This retrospective study included 27 patients with well-differentiated NET. 18F-FDG-PET images were evaluated by the maximum standardized uptake value (SUVmax). GLUT1, CA9, and pVHL were analyzed by immunohistochemistry.

Results: The NET were of pancreatic (n = 19), midgut (n = 4), duodenal (n = 1), esophageal (n = 1), rectal (n = 1), and pulmonary (n = 1) origin. Eight, 11, and 8 tumors were grade 1, 2, and 3, respectively. The mean/median Ki-67 index was 15/10% (1-60). The mean/median SUVmax was 6.2/5.2 (1.4-18.7). SUVmax correlated with greater tumor size (p = 0.03), higher expression of Ki-67 (p = 0.04), and lower expression of pVHL (p = 0.008). In the group of 16 NET with a low proliferative index (Ki-67 index <10%), 5/6 (83%) of the tumors with a high SUVmax had decreased pVHL expression (p = 0.0013).

Conclusion: This study confirms that 18F-FDG-PET uptake correlates with both tumor size and proliferation in well-differentiated NET, and it highlights a subset of low-grade but 18F-FDG-PET-positive NET related to sporadic inactivation of the VHL pathway.

Keywords: 18F-FDG positron emission tomography; Neuroendocrine tumors; Proliferation index; Von Hippel-Lindau protein.

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism
  • Carbonic Anhydrase IX / metabolism
  • Female
  • Fluorodeoxyglucose F18*
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neuroendocrine Tumors / diagnostic imaging*
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / surgery
  • Positron Emission Tomography Computed Tomography
  • Radiopharmaceuticals*
  • Retrospective Studies
  • Tumor Burden
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • Ki-67 Antigen
  • Radiopharmaceuticals
  • SLC2A1 protein, human
  • Fluorodeoxyglucose F18
  • Von Hippel-Lindau Tumor Suppressor Protein
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • VHL protein, human