Carbonic anhydrase IX is highly expressed in hereditary nonpolyposis colorectal cancer.
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.
Niemelä
Anssi M
AM
Department of Surgery, Jyväskylä Central Hospital, Keskussairaalantie 19, 40620 Jyväskylä, Finland.
Hynninen
Piritta
P
Mecklin
Jukka-Pekka
JP
Kuopio
Teijo
T
Kokko
Antti
A
Aaltonen
Lauri
L
Parkkila
Anna-Kaisa
AK
Pastorekova
Silvia
S
Pastorek
Jaromir
J
Waheed
Abdul
A
Sly
William S
WS
Orntoft
Torben F
TF
Kruhøffer
Mogens
M
Haapasalo
Hannu
H
Parkkila
Seppo
S
Kivelä
Antti J
AJ
D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007527:Isoenzymes; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases