Stains
Carbonic anhydrase IX

Author: Satbir Thakur, Ph.D. and Emeka Enwere, Ph.D. (see Authors page)

Revised: 27 June 2016, last major update June 2016

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PubMed Search: carbonic anhydrase ix
Cite this page: Carbonic anhydrase IX. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainscarbonicanhydraseix.html. Accessed December 7th, 2016.
Definition / General
  • Carbonic Anhydrase 9 (CAIX) is a zinc metalloenzyme and belongs to a family of enzymes that are involved in reversible hydration of carbon dioxide to form bicarbonate and hydrogen ions (Mol Phylogenet Evol 1996;5:50)
  • These enzymes are involved in various biological processes such as respiration, calcification, pH balance, bone resorption and formation of various body fluids like aqueous humor, cerebrospinal fluid, saliva, and gastric acid (NCBI)
Essential Features
Terminology
    Also known as:
  • Carbonic Anhydrase IX
  • Renal Cell Carcinoma-Associated Antigen G250
  • RCC-Associated Protein G250
  • RCC-Associated Antigen G250
  • Carbonate Dehydratase IX
  • Carbonic Dehydratase
  • Membrane Antigen MN
  • P54/58N
  • CA-IX
  • CAIX
  • PMW1
  • MN
  • EC 4.2.1.1
  • G250 (GeneCards)
Sites
  • Plasma Membrane
Pathophysiology
  • CAIX is overexpressed in a variety of solid tumors, but is underexpressed in normal tissues
  • CAIX promotes the growth of hypoxic tumors by maintaining an alkaline pH and generation of an acidic extracellular space which facilitates tumor cell invasion (Oncotarget 2012;3:84)
  • CAIX expression promotes cell cancer cell migration by competing with E cadherin for binding to β catenin, inactivation of Rho kinase and induction of EMT (Exp Cell Res 2003;290:332, J Cell Sci 2011;124:1077)
  • CAIX knockout mice have symptoms such as gastric hyperplasia of the glandular epithelium, cysts and depletion of pepsinogen secreting cells (Gastroenterology 2002;123:1889)
  • Aged CAIX null mice suffer from brain degenerative diseases but do not show increased tumorgenicity (Transgenic Res 2005;14:655 )
Uses by Pathologists
  • Breast: in breast cancer, high expression for CAIX can serve as an independent marker for poor prognosis for distant metastasis and overall survival (Cancer Res 2011;71:3364)
  • CNS: in glioblastoma, high expression of CAIX driven by HIF1α contributes to chemoresistance and metastasis by inducing an acidic environment (Curr Pharm Des 2010;16:3288)
  • Head and neck:
    • High stromal CAIX expression was found to be associated with increased nodal metastasis and reduced 5 year disease specific survival in surgically treated oral squamous cell carcinoma patients (Oral Oncol 2012;48:615)
    • Strong CAIX expression in head and neck tumors is associated with poor vascularization and poor response to chemotherapy (Clin Cancer Res 2001;7:3399)
  • Kidney: CAIX expression acts as a biomarker and can improve diagnostic accuracy for primary RCC as well as metastatic RCC patients (Clin Cancer Res 2003;9:802, Eur Urol 2010;58:75)
  • Stomach: increased expression of CAIX in gastric cancers is associated with an invasive phenotype (Gut 2005;54:920)
  • Treatment: due to its role in tumor survival and progression and metastasis and loss of expression in normal tissues, inhibition of CAIX is being considered as a viable target for cancer therapy and various monoclonal antibodies and small molecule inhibitors are currently being tested in experimental models and clinical trials
  • CAIX can serve as an endogenous marker for tumor hypoxia (Cancer Res 2001;61:8924)
Micro Images

Images hosted on other servers:
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CAIX staining in gastric cancer

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CAIX staining in normal
kidney and clear cell
renal carcinoma

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CAIX staining in normal stomach

Positive Stains
  • Normal duodenum, gallbladder, small intestine, stomach show high expression of CAIX (Protein Atlas)
Negative Stains
  • All other normal tissues stain negative for CAIX protein expression (Protein Atlas)