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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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.
Tumor cells in conventional clear cell RCC often show diffuse membranous positivity with CA-IX in a box-shape pattern (Figure 1, A).
19) The characteristic cup-shape immunohistochemical labeling for CA-IX in clear cell papillary RCC differs slightly from that of clear cell RCC with box-shape pattern (Figure 1, A).
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).
2 (100%, 96%), EMA, CA-IX, PAX-2 (100%), and progesterone receptor (0%) [15].
Therefore we can assume that useful immunohistochemical staining for EMA, CK7, and CA-IX may be helpful in establishing a more accurate diagnosis and differentiating other cystic lesions from MCRCC as we saw in our case.
9) Pancytokeratin staining can be patchy or even absent in a subset of CCRCCs, especially high-grade CCRCCs; in these cases, the presence of an unequivocal low-grade component and/or strong and diffuse, complete membranous CA-IX expression supports the diagnosis of CCRCC.
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.
In addition, t-RCC is typically negative for CA-IX (Figure 1, F) and shows variable expression of melanocytic markers (ie, HMB-45, Melan-A, among others) and the osteoclastic protein cathepsin K.
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.