title: Carbonic anhydrase IX expression correlates with FDG uptake by primary non-small cell lung cancer.
abstract: Tumor cells are characterized by an increased rate of glucose consumption and glycolysis. This increased glucose consumption leads to tumor acidification, which represents a major obstacle for several therapeutic strategies. Tumor cells have adapted to this acidification by upregulation of several H(+)-extruding transporter systems and proteins to cope with this compromised situation. One of these proteins is carbonic anhydrase IX (CA IX), which catalyzes the reversible hydration of carbon dioxide to carbonic acid outside the cell, leading to an acidic extracellular pH and a physiological intracellular pH. The aim of this article was to study semiquantitatively the expression of CA IX in non-small cell lung cancer (NSCLC) and to assess the existence of a possible relationship between CA IX expression and tumor FDG uptake, reflecting glucose metabolism. The levels and the extent of CA IX expression were estimated in immunohistochemical stained, formalin-fixed, paraffin-embedded tissue samples from 18 patients with NSCLC and compared with FDG uptake in FDG-PET imaging. We found a statistically significant correlation between CA IX Hscores and SUVmax and SUVmean values of the primary tumor. This relationship provides indirect evidence for cotranscription of glucose transporters and hexokinases that drive tumor hyperglycolysis and for CA IX governed by hypoxia-inducible factor-1 and suggests that, in the future, it may be possible to identify NSCLC patients who are most likely to benefit from CA IX targeting therapy on the basis of FDG-PET imaging.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Gilles
authors.initials: G
authors.lastname: Mees
authors.forename: Christel
authors.initials: C
authors.lastname: Vangestel
authors.forename: Rudi
authors.initials: R
authors.lastname: Dierckx
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Jan
authors.initials: J
authors.lastname: Van Meerbeeck
authors.forename: Christophe
authors.initials: C
authors.lastname: Van de Wiele
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D005947:Glucose