CA.1aj.9

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CA.1aj.9

A gene on chromosome 9p12 that encodes a carbonic anhydrase, a zinc metalloenzyme that catalyses the reversible hydration of carbon dioxide. Carbonic anhydrases participate in various biological processes, including respiration, calcification, maintaining acid-base balance and bone resorption, as well as producing aqueous humour, cerebrospinal fluid, saliva and gastric acid. CA9 is a transmembrane protein and the only known tumour-associated carbonic anhydrase isoenzyme, and may be involved in cell proliferation and transformation.

Molecular pathology
CA9 is expressed in all clear-cell type renal cell carcinomas, but is not expressed in normal kidney or most other normal tissues.
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Immunohistochemical stains were positive for CD10, PAX8, and carbonic anhydrase 9/IX (CA-IX) and negative for CK7.
Immunohistochemistry is helpful in differentiating these entities as CA-IX and CD10 are most frequently expressed in CCRCC than Mullerian CCC, whereas CK7, Napsin-A, and methylacyl-coenzyme-A racemase (AMACR) show a reverse pattern of expression [3].
(d) Tumor cells showing complete membranous immunopositivity for CA-IX (x200).
The tumor cells were positive for paired box gene 8 (PAX8), transcription factor E3 (TFE3), human melanoma black 45 (HMB45), [alpha]-methylacyl coenzyme A racemase (AMACR), and CD10, and were negative for keratin (AE1/AE3/CAM5.2), epithelial membrane antigen (EMA), cytokeratin 7 (CK7), carbonic anhydrase IX (CA-IX), CD117, melanoma antigen recognized by T cells 1 (Mart-1), microphthalmia-associated transcription factor (MiTF) and Melan-A.
(5) When dealing with tumors with clear cell features and morphology not typical for clear cell RCC or when limited material is available, we usually perform a panel of markers in various combinations that includes CA-IX, CK7, AMACR, CD117, transcription factor E3 and transcription factor EB (TFE3/TFEB), and HMB45.
Two important tumor-associated membrane carbonic anhydrase iso-zymes CA-IX and CA-XII are documented in literature.
There are many effective inhibitors of CAs, most of classical sulfonamides/sulfamates CA inhibitors and their derivatives, such as ethoxzolamide (EZA), acetazolamide (AZA), do not have a good selectivity of CA-IX, over the sulfonamide-avid against iso-zyme CA-II [8-10].
They observed that the cysts lined epithelial cells and the clear tumor cell clusters were positive for epithelium markers like CKpan (19/19), EMA (16/19) and CK7 (15/19), CA-IX (17/19) and PAX8 (15/19), and a low percentage staining for CD10 (7/19).
Another study assessed the immunohistochemical staining characteristics, of MRCC versus control cases, showing the following results, respectively: CD10 (63% versus 96%), CK7 (92% versus 38%), [alpha]-methylacyl-CoA-racemase (21% versus 67%), vimentin (58% versus 33%), estrogen receptor (8% versus 8%), CAM 5.2 (100%, 96%), EMA, CA-IX, PAX-2 (100%), and progesterone receptor (0%) [15].
(6) Typically, CCRCC expresses pancytokeratin, epithelial membrane antigen, CD10, and carbonic anhydrase IX (CA-IX; diffuse, complete membranous staining; Figure 1, B); a-methylacyl-coenzyme A racemase (AMACR) expression is variable, CK7 expression is usually negative or focal, and CCRCC is typically negative for CD117 expression.
Usually, CA-IX is also strongly and diffusely positive but shows a unique basolateral ("cuplike") membranous staining pattern, with a relative lack of staining at the apical membrane (Figure 1, D); this is in contrast to CA-IX expression in CCRCC, which is strong and diffuse in a complete membranous pattern.
Immunohistochemical Comparison of Clear Cell Adenocarcinoma of the Urinary Bladder, Clear Cell Carcinoma of the Ovary, and Clear Renal Cell Carcinoma Clear Cell Adenocarcinoma Clear Cell Clear Renal Immunohistochemical of the Urinary Carcinoma Cell Stain Bladder of the Ovary Carcinoma Cytokeratin AE1/AE3 + + + CAM 5.2 + + + Cytokeratin 7 + + - Cytokeratin 20 [+ or -] - - EMA + + + CEA (polyclonal) + [+ or -] - Leu-M1 + + + CA 125 + [+ or -] - B72.3 - + - Vimentin - - + RCC - - + CD10 - - + CA-IX - - + Abbreviations: CA-IX, carbonic anhydrase isoenzyme IX; CEA, carcinoembryonic antigen; EMA, epithelial membrane antigen; RCC, renal cell carcinoma; +, positive; -, negative; [+ or -], equivocal.