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Carbonic Anhydrase IX Is Highly Expressed in Hereditary Nonpolyposis Colorectal Cancer

Departments of ¹ Surgery and ² Pathology, Jyväskylä Central Hospital, Jyväskylä, Finland; ³ Institute of Medical Technology and Departments of ⁴ Pathology, ⁵ Obstetrics and Gynecology, and ⁶ Neurology, University of Tampere and Tampere University Hospital, Tampere, Finland; ⁷ Department of Medical Genetics and Cancer Biology Research Program, University of Helsinki, Helsinki, Finland; ⁸ Center of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic; ⁹ Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri; and ¹⁰ Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Aarhus N, Denmark

Requests for reprints: Antti J. Kivelä, Department of Surgery, Jyväskylä Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, Finland. Phone: 358-50-324-7762; Fax: 011-358-14-269-3626. E-mail: antti.j.kivela{at}fimnet.fi

Carbonic anhydrase (CA) II, CA IX, and CA XII are expressed in various neoplasias and have been linked to tumorigenesis. We examined their expression in three different groups of colorectal cancer [i.e., microsatellite stable (MSS), microsatellite instable (MSI), and hereditary nonpolyposis colorectal cancer (HNPCC)]. First, we analyzed gene expression profiles of 113 specimens by a microarray method to study the expression of various CA isozymes in the subgroups of colorectal cancer. The results indicated that mRNAs for CA II and CA XII are down-regulated and CA IX mRNA is up-regulated in all three tumor categories when compared with the normal tissue. The up-regulation of CA IX was greatest in the HNPCC group. For more information, 77 specimens were immunohistochemically stained to study the levels of CA II, CA IX, and CA XII. Immunohistochemical analyses further confirmed that the subgroups express CA II, CA IX, and CA XII differentially, and the HNPCC tumors express high levels of CA IX. Expression of these CAs did not correlate to Dukes stage or grade of differentiation. Our results show that CAs are differentially expressed in the subgroups of colorectal cancer, and CA IX expression seems to be very high in most cases of HNPCC. CA IX could be a potential diagnostic and therapeutic target in HNPCC. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1760–6)