Carbonic Anhydrase IX Expression In Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Radiology / Nuclear Medicine
Article Date: 21 Feb 2010 - 1:00 PDT


UroToday.com - Tumor hypoxia plays a role in tumor progression and chemotherapy resistance through reduced apoptosis, increased proliferation and angiogenesis. Hypoxic cell metabolism switches to anaerobic glycolysis and the production of acidic metabolites that facilitate cell survival and tumorigenesis. The pH of solid tumors is more acidic than normal tissue and impairs the uptake of weakly basic chemotherapeutic drugs. The group of Professor R. W. G. Watson in Dublin, Ireland investigated whether the hypoxic factor carbonic anhydrase IX (CA IX) is involved in prostate cancer (CaP) tumorigenesis.

CA IX is upregulated in hypoxia in response to HIF 1-a binding to the hypoxia responsive element on the CA IX promoter. CA IX in other tumors has a pro-survival function by maintaining intra-cellular pH high and extra-cellular pH low thus ensuring cell growth and invasion through activation of proteolytic and signal transduction pathways. CA IX expression can be measured by immunohistochemical staining and inhibitors against CA IX are in development.

In this report, tissue from 59 patients who underwent radical prostatectomy was used to make tissue microarrays (TMAs) and for full sectioning. In the TMAs, there were 189 areas of histologically benign tissue, 130 areas of Gleason grade 3, 93 areas of Gleason grade 4, and 40 areas of Gleason grade 5. Both benign areas and all areas of Gleason grade CaP did not stain for CA IX. There was also no evidence of expression in the full sections.

This suggests that CaP hypoxia does not involve the CA IX pathway, and that CA IX is likely neither a useful marker nor target in CaP.

Smyth LG, O'Hurley G, O'Grady A, Fitzpatrick JM, Kay E, Watson RW

Prostate Cancer Prostatic Dis. 2009 Dec 29. (Epub ahead of print)
10.1038/pcan.2009.58

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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