BERKELEY, CA (UroToday.com) - Carbonic anhydrase IX is a metalloenzyme that is upregulated in hypoxic conditions. This protein is of interest to urologists and other medical professionals treating genitourinary malignancies due to its high expression in clear cell renal cell carcinoma.
|"Carbonic anhydrase IX is an exceptional marker for clear cell renal cell carcinoma, with numerous possible diagnostic and therapeutic functions."|
In the recent journal article “Expression of Carbonic Anhydrase IX in Genitourinary and Adrenal Tumours,” I describe the immunohistochemical membranous expression of carbonic anhydrase IX in non-neoplastic tissue and tumors from all organs relevant to urologists including the kidney, bladder/renal pelvis/ureter, prostate, testis and adrenal gland. Within the kidney, non-neoplastic renal tubules do not demonstrate membranous expression of carbonic anhydrase IX. Robust, consistent expression was seen in clear cell renal cell carcinoma, including biopsies, primary resections, and metastatic lesions. As such, carbonic anhydrase IX is an excellent marker for clear cell renal cell carcinoma. The majority of papillary renal cell carcinoma also expresses carbonic anhydrase IX, however this expression is often in a minority of cells and with weak expression intensity. It is important to note that the newly described entity, clear cell papillary renal cell carcinoma, shows similar strong, diffuse expression as clear cell renal cell carcinoma. Translocation associated renal cell carcinoma, which can clinically and histologically mimic clear cell renal cell carcinoma, does not express carbonic anhydrase IX.
Tumors primary to the bladder, renal pelvis and ureter displayed inconsistent expression of carbonic anhydrase IX with the exception of clear cell adenocarcinoma, in which all cases were positive. Non-neoplastic adrenal tissue and adrenal tumors had minimal expression of carbonic anhydrase IX. Within the testicle, germ cell tumors were negative but Sertoli cell tumor had variable expression.
Carbonic anhydrase IX has a potential role for physicians in diagnosing primary and metastatic tumors via serum, urine or imaging. Diagnostic positron emission tomography (PET) imaging using the cG250 antibody allows for the visualization of clear cell renal cell carcinoma. Knowledge of carbonic anhydrase IX expression in other organs will facilitate better interpretation of cG250 PET. Additionally, clear cell renal cell carcinoma often has late metastases, particularly to the lung.
In a subsequent study, we demonstrate that in addition to clear cell renal cell carcinoma metastatic to the lung, all mesothelial lesions including pleural mesothelioma, strongly expresses carbonic anhydrase IX.1
In summary, carbonic anhydrase IX is an exceptional marker for clear cell renal cell carcinoma, with numerous possible diagnostic and therapeutic functions. To date, the only malignancies which show similar consistent strong and diffuse membranous immunohistochemical expression include clear cell papillary renal cell carcinoma and pleural mesothelioma.
- Ramsey ML, Yuh BJ, Johnson MT, Yeldandi AV, Zynger DL. Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung. Virchows Arch. 2012 Jan;460(1):89-93.
Debra L. Zynger, MS, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Address correspondence and reprint requests to:
Debra L. Zynger, MS, MD
Department of Pathology
The Ohio State University Medical Center
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Columbus, OH 43210
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