Carbonic anhydrase II. A novel biomarker for gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) are clinically distinct mesenchymal tumors, which generally result from expression of mutant KIT or PDGFRA receptor tyrosine kinase oncogenes. Most GISTs feature strong expression of KIT that serves as a crucial diagnostic adjunct. However, a subset of tumors lacks KIT expression and otherwise may also be difficult to distinguish from other sarcomas, including leiomyosarcoma. Because various carbonic anhydrase (CA) isozymes have been identified as potential treatment targets against different cancers, we evaluated CA II expression in 175 GISTs. Western blotting experiments indicated that CA II is highly expressed in GIST cell lines. Immunohistochemically, 95% of GISTs showed positive signal. The CA II expression in GISTs did not correlate with particular KIT or PDGFRA mutation types. CA II immunoreactivity was absent or low in other mesenchymal tumor categories analyzed. High CA II expression was associated with a better disease-specific survival rate than low or no expression (Mantel-Cox test, P<0.0001). The present results indicate that CA II is overexpressed in most GISTs, is quite selective to this tumor type among mesenchymal tumors, and therefore might be a useful biomarker in diagnostics.
Parkkila
Seppo
S
Department of Anatomy, University of Tampere and Tampere University Hospital, Tampere, Finland. Seppo.Parkkila@uta.fi
Lasota
Jerzy
J
Fletcher
Jonathan A
JA
Ou
Wen-Bin
WB
Kivelä
Antti J
AJ
Nuorva
Kyösti
K
Parkkila
Anna-Kaisa
AK
Ollikainen
Jyrki
J
Sly
William S
WS
Waheed
Abdul
A
Pastorekova
Silvia
S
Pastorek
Jaromir
J
Isola
Jorma
J
Miettinen
Markku
M
D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*
D014408:Biomarkers, Tumor; D024402:Carbonic Anhydrase II