title: Carbonic anhydrase IX expression in clear cell renal cell carcinoma: an immunohistochemical study comparing 2 antibodies.
abstract: Carbonic anhydrase IX (CAIX)-a protein maintaining intracellular and extracellular pH-reportedly also influences regulation of cell proliferation, oncogenesis, and tumor progression. Its expression is von Hippel-Lindau-hypoxia inducible factor pathway dependent. Immunohistochemical (IHC) studies show that CAIX is diffusely overexpressed in clear cell renal cell carcinoma (CRCC), making it a potentially important differential diagnostic marker. Prognostically, low CAIX expression reportedly indicates poor survival and low response to interleukin therapy in CRCC. Most IHC studies have used clone M75 as the primary antibody, which is not commercially available. We evaluated a new commercially available antibody (clone NB100-417) to assess its expression in CRCC and compared its results with M75. On a tissue microarray of CRCC, IHC staining was performed using both antibodies. The immunoreactivity was graded as 0; 1+, 1% to 25%; 2+, 26% to 50%; and 3+, >50% tumor cells immunoreactive. Ninety-one out of ninety-five (96%) cases showed similar staining grade with excellent agreement (kappa=0.65, weighted kappa=0.75). Grade 3+ expression of CAIX was observed in 89 (94%) cases each, with both antibodies. Both antibodies produced intense membrane-predominant expression, limited to tumor cells. More than 95% of the tumors with low nuclear grade, compared with 84% and 88% of tumors with high nuclear grade, showed 3+ expression using both antibodies. Thus, most CRCC show strong and diffuse expression of CAIX, and the expression is comparable using both antibodies. Therefore, similar to the clone M75, NB100-417 can be used as a diagnostic and potentially a prognostic marker in CRCC, with the advantage of its commercial availability.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Hikmat A
authors.initials: HA
authors.lastname: Al-Ahmadie
authors.forename: Darym
authors.initials: D
authors.lastname: Alden
authors.forename: Li-Xuan
authors.initials: LX
authors.lastname: Qin
authors.forename: Semra
authors.initials: S
authors.lastname: Olgac
authors.forename: Samson W
authors.initials: SW
authors.lastname: Fine
authors.forename: Anuradha
authors.initials: A
authors.lastname: Gopalan
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Satish K
authors.initials: SK
authors.lastname: Tickoo
mesh_terms: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000201:enzymology*; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C475102:M75 monoclonal antibody; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases