Carbonic Anhydrase IX (CA IX) Antibody Review





  • an endogenous (intrinsic) hypoxia marker in several models. PMID: 17172824, PMID: 16513206

  • a renal cell carcinoma (RCC)-specific tumor protein. PMID: 17146628

  • an interesting target for anticancer drug development. PMID: 16996620

  • a transmembrane protein whose expression is strongly induced by hypoxia in a broad spectrum of human tumours. PMID: 16278664

  • a stable marker of current or previous chronic hypoxia but influenced by nonhypoxic stimuli. PMID: 15752902

  • a membrane-associated carbonic anhydrase (CA), strongly induced by hypoxia. CAIX is overexpressed in a variety of tumor types and associated with increased metastasis and poor prognosis. PMID: 15342400

  • one of the most inducible and most uniformly induced genes and because of its stability and membrane location provides a reliable histochemical marker of hypoxia. PMID: 14712082

  • regulated via hypoxia-inducible factor 1, is a useful intrinsic marker of tumor hypoxia. PMID: 14654550

  • Tumour-associated protein carbonic anhydrase IX (CA IX) has two major forms. One is a cell-associated, transmembrane protein seen on Western blots as a twin band of 54/58 kDa, expressed in gastric mucosa and in several types of cancer. The other is a soluble protein s-CA IX of 50/54 kDa, which is released into the culture medium or into the body fluids, most likely by proteolytic cleavage of the extracellular part from transmembrane and intracellular sequences. PMID: 12966427

  • a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer. PMID: 12560438

  • an integral membrane protein and a member of the alpha class of carbonic anhydrases that includes the human and animal enzymes. PMID: 11676494

  • a transmembrane enzyme with an extracellular active site, is involved in the reversible metabolism of the carbon dioxide to carbonic acid. PMID: 11691824

Normal Expression

  • Normal human brain tissue shows only slight or no expression of CA IX. PMID: 16428489

  • a hypoxia-inducible enzyme, which is expressed in the human and rodent gastrointestinal tract and overexpressed in several different tumors. PMID: 16245156

  • Expression of CA IX is normally restricted to the mucosa of alimentary tract, but on the other hand, it takes place in a high percentage of human cancers derived from tissues which are normally CA IX-negative. PMID: 15809767

  • Immunohistochemical (IHC) analysis showed strong staining in the gastric mucosa. Moderate reactions were seen in the colon enterocytes and pancreatic acini. The expression pattern of CA IX was similar in certain human and rodent tissues, although some differences existed, especially in the gut epithelium. PMID: 15385577

  • CA IX was highly expressed in the normal gastric mucosa and remained positive in many gastric tumors. PMID: 12854129

  • expressed in the basolateral plasma membrane of normal biliary epithelial cells, but not in hepatocytes. PMID: 11690711

  • both CA IX and XII are unevenly expressed in the ductal and acinar compartments of the human pancreas. PMID: 11083462

  • expressed in normal alimentary tract in a tissue-specific manner. PMID: 11771176

  • Specific staining for CA XII was present in the basolateral plasma membrane of the epithelial cells in the efferent ducts, predominantly in the non-ciliated cells. PMID: 11420383

Abnormal Expression

  • a cell surface tumor-associated antigen expressed by most clear cell renal cell carcinomas (RCCs). PMID: 17095063

  • highly overexpressed in many types of cancer. Its expression, which is regulated by the HIF-1 transcription factor, is strongly induced by hypoxia and correlates with a poor response to classical chemo- and radiotherapies. PMID: 16996620

  • pre-dominantly expressed in tumors with poor prognosis and its transcription and activity are induced by hypoxia. PMID: 16964400

  • is a membrane isoenzyme, the overexpression of which is associated with clear cell carcinoma of the kidney. Its overexpression is restricted mainly to cancer, as it is absent in corresponding normal tissues making it a potential cancer biomarker. PMID: 16310354

  • can be induced by hypoxia in vitro and shows an immunohistochemical expression pattern that is predominantly found in perinecrotic tumor areas and correlates with exogenous markers of hypoxia, such as pimonidazole. PMID: 16243791

  • Carbonic anhydrase IX expression is observed in both ductal epithelial and cancer cells of the pancreas. PMID: 14535878

  • CA IX was detected by IHC in 12/26 (46%) malignant tissues, 4/36 (11%) benign lesions, but not in 10 normal breasts. PMID: 12115877

Expression Alteration 

  • acidosis increases the CA IX expression via a hypoxia-independent mechanism that operates through modulation of the basic CA9 transcriptional machinery. PMID: 16964400

  • CA IX carbonic anhydrase is a hypoxia-inducible tumor-associated antigen which is overexpressed in dense HeLa cells. PMID: 12937836


  • comparison of CAIX and pimonidazole will allow for the detection of reoxygenation. PMID: 17172824

  • a useful biomarker for predicting poor prognosis of astrocytic tumors. It may also be a promising target molecule for the improvement of therapeutic interventions in astrocytomas. PMID: 16428489

  • a tumor-associated transmembrane isoform of the carbonic anhydrase with a high enzyme activity and a functional involvement in the pH regulation and cell adhesion. PMID: 15754010

  • CAIX plays an important role in the growth and survival of tumor cells under normoxia and hypoxia, making it a potential target for cancer therapy, but is not involved in invasion. PMID: 15342400

  • CA IX expression may detect not only actually hypoxic tumor regions, but also the regions affected by hypoxia and adverse microenvironmental stresses before biopsy or tumor removal. PMID: 15010840

  • CA IX has a capacity to modulate E-cadherin-mediated cell adhesion via interaction with beta-catenin, which could be of potential significance in hypoxia-induced tumor progression. PMID: 14567991

  • MN/CA IX is a useful marker for the differentiation between preneoplastic lesions and bronchial non-small cell lung cancer in the lung. PMID: 10573225

  • The co-occurrence of MN/CA IX and Ki-67 in the same tumor cells indicates its potential for use as a marker of increased proliferation in the colorectal mucosa. PMID: 9665489

  • CA IX expression status was the most reliable hypoxia marker for predicting tumor aggressiveness. PMID: 15935515

  • M75 mAb, recognizing CA IX antigen, has targeting properties which could be potentially useful in radioimmunodetection or radioimmunotherapy of human cervical carcinomas and derived metastases. PMID: 12687273

Diagnostic and Therapeutic Value

  • Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). PMID: 17213826

  • CA IX expression is strongly associated with tumor progression and indicates a poor prognosis for patients with stages I+II lung adenocarcinoma. PMID: 17030461

  • CA IX expression, rather than VEGF positivity in tumors, enables the identification of a subpopulation, characterized by a more aggressive behavior and a poorer prognosis. PMID: 16495697

  • CAIX expression seems to be an important predictor of outcome in renal cell carcinoma patients receiving IL-2-based therapy and may enhance prognostic information obtained from pathology specimens. PMID: 15897568

  • CA IX expression of tumor cells may be an indicator for poor disease-free survival in early-stage non-small-cell lung cancer (NSCLC). PMID: 15585626

  • a potential intrinsic marker of hypoxia, predicts for poor prognosis in patients with deep, large, high-grade soft tissue sarcoma. PMID: 15240538

  • Ki67and CAIX are useful prognostic biomarkers for RCC that improve the survival prediction and classification of kidney cancer. PMID: 15126876

  • CA IX is a potential target for future therapy in head and neck squamous cell carcinoma (HNSCC). PMID: 11431368

  • expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. PMID: 17233814

  • The expression of the tumor-specific marker CA9 in the peripheral blood is associated with decreased disease-free survival in patients with renal cortical tumors. This is the first study reporting on the prognostic value of this peripheral blood-based tumor marker for kidney tumors. PMID: 16698354

  • patients with low CA9 levels benefit more from adjuvant treatment than do patients with high levels. Thus, the determination of CA9 levels could aid in the selection of patients who will not benefit from adjuvant therapy, and whose prognosis will more likely improve with other treatment modalities. PMID: 12865916

  • Stratification of patients undergoing radical radiotherapy using the CA9/MVD model may be useful for the individualization of therapeutic strategies combining antiangiogenesis and hypoxia targeting with radiotherapy. PMID: 11705854

  • CA9 is a significant molecular marker in renal clear cell carcinomas. Decreased CA9 expression is independently associated with poor survival. CA9 can be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CA9 targeted therapies. PMID: 15711113

  • expression of the MN/CA9 antigen is indeed a discriminator of significant lesions in AGUS Pap smear diagnoses. PMID: 10699902

  • MN/CA9 expression is a potential diagnostic biomarker of renal cell carcinoma (RCC), especially the clear-cell type, and can be targeted using molecular biological techniques. PMID: 10368188

  • MN/CA9 protein expression might have an important clinical utility in the early detection and treatment of renal cell carcinoma (RCC). PMID: 9230182

  • CA IX is, however, a weaker prognostic and predictive factor than HIF-1alpha, and its association with HIF-1alpha does not modify the survival curve neither response to therapy, compared to HIF-1alpha alone. PMID: 17245699

  • CA IX is marker of poor prognosis in premenopausal breast cancer patients and it is an independent predictor of survival in patients with one to three positive lymph nodes. As all these patients received locoregional radiation therapy, CA IX may be associated with resistance to radiotherapy. PMID: 17085655



Flow Cytometry

  • The expression of G250/mn/CA9 antigen by flow cytometry: its possible implication for detection of micrometastatic renal cancer cells. PMID: 11205923


  • Standard immunohistochemical techniques were used to study CA IX expression in 134 patients who underwent curative resection for adenocarcinoma of the lung at our hospital between January 1995 and December 1996. PMID: 17030461

  • We evaluated the immunohistochemical expression of CA IX and VEGF on paraffin-embedded material of 154 resection specimens: 39 esophageal, 73 cardiac, and 42 distal gastric adenocarcinomas (UICC classification). PMID: 16495697

  • Using real-time PCR and immunohistochemistry, we have examined the expression of carbonic anhydrase isozymes (CA) I, II, III, IV, IX, XII, XIII and XIV in the brain, kidney, stomach and colon of the wild-type, CA II-deficient (Car2-/-), and CA IX deficient (Car9-/-) mice. PMID: 16396925

  • We investigated the immunohistochemical pattern of distribution of CA IX in a small series (14 cases) of RCCs. PMID: 15500003

  • Immunohistochemical analysis using a CAIX and a Ki67 monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 224 patients treated with nephrectomy for clear cell renal carcinoma. PMID: 15126876

  • Immunohistochemistry was used to examine expression of CA IX in archival tissues of patients included in various therapeutic trials for transitional cell carcinoma (TCC) of the bladder. PMID: 15069539

  • CA IX expression was immunohistochemically detected in 2 independent study groups, totaling 184 patients, and correlated with tumor characteristics, angiogenesis related parameters and patient outcome by univariate analysis. PMID: 14572156

  • Immunohistochemical analysis using a CAIX monoclonal antibody was performed on tissue microarrays constructed from paraffin-embedded specimens from patients (N = 321) treated by nephrectomy for clear cell RCC. PMID: 12576453

  • CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. PMID: 11522632

  • CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. PMID: 11504747

  • Expression of CA9 and CD34, an endothelial cell marker, was examined in serial paraffin-embedded sections by immunohistochemistry in 25 grade 1, 17 grade 2, and 20 grade 3 meningiomas. PMID: 17200340

  • Tissue from pre-RT biopsies performed in 198 of 918 patients recruited was analyzed for the immunohistochemical expression of HIF-2 and CA9. PMID: 16418497

  • Expression of CA9, IdUrd labeling, and colocalization between IdUrd and CA9 was examined by immunohistochemistry in biopsies of head and neck squamous cell carcinomas. PMID: 15671533

  • Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/CA IX, with potential value as a marker of cell proliferation. PMID: 9665489

  • Immunohistochemistry of carbonic anhydrase isozyme IX (MN/CA IX) in human gut reveals polarized expression in the epithelial cells with the highest proliferative capacity. PMID: 9524195

Western Blot

  • The expression of CA IX and XII was examined by immunoperoxidase staining method and western blotting. PMID: 15488153

  • Expression of CA IX was determined by immunoblotting in three HNSCC cell lines grown in normoxia and hypoxia (pO(2) 0.1%) and three paired tumor and normal tissue samples of HNSCC. PMID: 11431368

  • Western blotting and immunohistochemical analyses of human and animal tissues were performed using CA IX-specific monoclonal antibody and rabbit antiserum to human CA II. PMID: 9024293

  • Using gastric cancer cell lines and tissues, we studied expression of Ca9 by western blot analysis, immunohistochemistry, and polymerase chain reaction. PMID: 15951534

  • Western blot analysis from efferent duct samples revealed specific bands for CA IX and CA XII, confirming that the immunohistochemical stainings represent these isozymes. PMID: 11420383