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.