Introduction: Carbonic anhydrase isoform IX (CA IX) is a mammalian enzyme that assists in the inter-conversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions to maintain acid-base balance in blood and tissues. Carbonic anhydrase IX has become an important marker for various cancers and is over-expressed in many cancers. Its expression is strongly induced by hypoxia and correlates with a poor response to classical therapies and is associated with increased metastasis and poor prognosis. By tissue analysis, CAIX has been found to be overexpressed in a high percentage of clear cell renal cell carcinomas (RCC). There are many reports of CAIX expression by immunohistochemistry (IHC) in the literature, but an assortment of antibodies are used, along with different antigen retrieval systems and procedures, leading to a lack of standardization. Materials and Methods: We have developed a standardized IHC test using the M75 monoclonal antibody (mab) that detects CAIX in formalin-fixed paraffin-embedded (FF-PE) tissues. This Research Use Only (RUO) test works without the use of any type of antigen retrieval. The scoring system is based on the percentage of cells that are positive for CAIX staining as well as the intensity of that staining. In addition, only membrane staining of CAIX is considered positive. Results: We have analyzed a number of normal and cancer tissues using both tissues and tissue microarrays (TMA). Data with normal tissues showed that 100% of stomach and 12% of colon are positive for CAIX staining. In addition, when examining tumor tissues, we found that >90% of colon and esophageal tumors were positive for CAIX staining.$$table_{02631489-AA06-4AC6-88C3-735E3C033589}$$ Conclusions: This study describes the first standardized IHC kit utilizing the M75 mab for detection of CAIX in FF-PE tissue sections. It is anticipated that the availability of this test will assist in the detection of CAIX positive tumors and perhaps aid in the development of anti-angiogenic or anti-hypoxic cancer therapies.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 244.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009