Carbonic anhydrase IX expression in clear cell renal cell carcinoma: An immunohistochemical study comparing 2 antibodies Journal Article


Authors: Al-Ahmadie, H. A.; Alden, D.; Qin, L. X.; Olgac, S.; Fine, S. W.; Gopalan, A.; Russo, P.; Motzer, R. J.; Reuter, V. E.; Tickoo, S. K.
Article 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 (κ=0.65, weighted κ=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. © 2008 Lippincott Williams & Wilkins, Inc.
Keywords: immunohistochemistry; controlled study; human tissue; protein expression; unclassified drug; major clinical study; cancer grading; tumor markers, biological; immunoreactivity; kidney carcinoma; kidney neoplasms; antibodies, monoclonal; antigens, neoplasm; carbonate dehydratase ix; carcinoma, renal cell; tissue microarray; antibody; carbonic anhydrase ix; carbonic anhydrases; clear cell renal cell carcinoma; commercially available; m75 antibody; nb100 417 antibody
Journal Title: American Journal of Surgical Pathology
Volume: 32
Issue: 3
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2008-03-01
Start Page: 377
End Page: 382
Language: English
DOI: 10.1097/PAS.0b013e3181570343
PUBMED: 18300814
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 22" - "Export Date: 17 November 2011" - "CODEN: AJSPD" - "Source: Scopus"
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MSK Authors
  1. Paul Russo
    581 Russo
  2. Robert Motzer
    1243 Motzer
  3. Semra Olgac
    98 Olgac
  4. Satish K Tickoo
    485 Tickoo
  5. Li-Xuan Qin
    191 Qin
  6. Anuradha Gopalan
    417 Gopalan
  7. Samson W Fine
    462 Fine
  8. Victor Reuter
    1228 Reuter
  9. Darym A Alden
    9 Alden