title: Carbonic anhydrase II. A novel biomarker for gastrointestinal stromal tumors.
abstract: 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.
authors.affiliation: Department of Anatomy, University of Tampere and Tampere University Hospital, Tampere, Finland. Seppo.Parkkila@uta.fi
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lasota
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Ou
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kivelä
authors.forename: Kyösti
authors.initials: K
authors.lastname: Nuorva
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Parkkila
authors.forename: Jyrki
authors.initials: J
authors.lastname: Ollikainen
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
authors.forename: Abdul
authors.initials: A
authors.lastname: Waheed
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastorekova
authors.forename: Jaromir
authors.initials: J
authors.lastname: Pastorek
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
mesh_terms: 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*
chemical_list: D014408:Biomarkers, Tumor; D024402:Carbonic Anhydrase II