Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy.
BACKGROUND
The clinical management of patients with renal cell carcinoma (RCC) remains difficult, and the development of new diagnostic, prognostic, and therapeutic tools is still required.


OBJECTIVE
To review the current knowledge on the RCC-associated antigen carbonic anhydrase IX (CAIX) and provide evidence for how this antigen may aid in the clinical management of RCC.


METHODS
Clinical papers describing diagnostic, prognostic, and/or therapeutic applications of CAIX in RCC were selected from the Pubmed database. The search was manually augmented by reviewing the reference lists of articles.


RESULTS
Expression of CAIX is regulated by the Von Hippel Lindau (VHL) protein (pVHL). Because of the invariable VHL mutational loss in clear-cell RCC (ccRCC) patients, CAIX expression is ubiquitous in ccRCC. Determination of CAIX expression in nephrectomy specimens of RCC patients improves prognostic accuracy; high CAIX expression appears to correlate with a favourable prognosis and a greater likelihood of response to systemic treatment for metastatic disease. Therefore, CAIX expression might be used to stratify metastatic ccRCC (mRCC) patients for systemic treatment. When incorporated into the RCC nomogram, CAIX expression seems to improve diagnostic accuracy for primary RCC as well as mRCC patients, but further evidence is required. Clinical studies with the CAIX-specific monoclonal antibody (mAb) cG250 have provided unequivocal evidence that ccRCC lesions can be imaged with radiolabeled cG250. Results are awaited of a large, randomised trial that aims to establish the value of cG250 imaging for primary RCC. The outcome of another large, placebo-controlled study is awaited to establish the usefulness of CAIX-targeted therapy in the adjuvant setting. Therapeutic trials with high-dose radiolabeled cG250 and CAIX-loaded dendritic cells in mRCC patients are still in phase 1 or 2.


CONCLUSIONS
CAIX improves diagnostic accuracy and is an attractive target for imaging of and therapy for ccRCC.
Stillebroer
Alexander B
AB
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. a.stillebroer@uro.umcn.nl
Mulders
Peter F A
PF
Boerman
Otto C
OC
Oyen
Wim J G
WJ
Oosterwijk
Egbert
E
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000628:therapy*; D009154:Mutation; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C106533:G250 monoclonal antibody; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases