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Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung

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Abstract

High immunohistochemical expression of carbonic anhydrase IX (CAIX) is found in clear cell renal cell carcinoma (ccRCC), but no studies have assessed CAIX in metastatic ccRCC (mccRCC) of the lung. As 75% of patients with mccRCC show lung involvement, characterization of protein expression in these lesions is warranted. This investigation analyzed CAIX immunohistochemical expression in pulmonary/pleural tumors including mccRCC (n = 22), mesothelioma (n = 19), squamous cell carcinoma (n = 27), small cell carcinoma (n = 9), and adenocarcinoma (n = 49), as well as other mesothelial lesions (n = 4). Membranous immunoreactivity was semiquantitatively evaluated for percent of cells stained and intensity. All cases of mccRCC (1+, 4.5%; 3+, 95.5%) and mesothelioma (2+, 10.5%; 3+, 89.5%) expressed CAIX. Most cases of lung squamous cell carcinoma (0, 11.1%; 1+, 25.9%; 2+, 22.2%; 3+, 40.7%) and small cell carcinoma were reactive (0, 11.1%; 1+, 22.2%; 2+, 33.3%; 3+, 33.3%), while CAIX was detected less frequently in pulmonary adenocarcinoma (0, 61.2%; 1+, 16.3%; 2+, 12.2%; 3+, 10.2%). In addition, CAIX was positive in adenomatoid tumor (3+, 100%) and mesothelial hyperplasia (3+, 100%). We demonstrate that CAIX is sensitive for mccRCC within the lung and a novel immunohistochemical marker for mesothelial proliferations, notably mesothelioma. Variable immunoreactivity is present among primary pulmonary epithelial tumors. Knowledge of expression overlap between these entities may prevent an incorrect interpretation of immunohistochemical results, particularly when limited tissue is available. As new carbonic anhydrase inhibitors are being evaluated, testing additional tumors for CAIX may lead to novel treatment options.

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References

  1. Stillebroer AB, Mulders PFA, Boerman OC et al (2010) Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy. Eur Urol 58:75–83

    Article  PubMed  CAS  Google Scholar 

  2. Kon-no H, Ishii G, Nagai K et al (2006) Carbonic anhydrase IX expression is associated with tumor progression and a poor prognosis of lung adenocarcinoma. Lung Cancer 54(3):409–418

    Article  PubMed  Google Scholar 

  3. Leibovich BC, Sheinin Y, Lohse CM et al (2007) Carbonic anhydrase IX is not an independent predictor of outcome for patients with clear cell renal cell carcinoma. J Clin Oncol 25:4757–4764

    Article  PubMed  Google Scholar 

  4. Malentacchi F, Simi L, Nannelli C et al (2009) Alternative splicing variants of carbonic anhydrase IX in human non-small cell lung cancer. Lung Cancer 64:271–276

    Article  PubMed  Google Scholar 

  5. Patard J, Fergelot P, Karakiewicz PI et al (2009) Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. Int J Cancer 123(2):395–400

    Article  Google Scholar 

  6. Ivanov S, Liao SY, Ivanova A et al (2001) Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Am J Pathol 158(3):905–919

    Article  PubMed  CAS  Google Scholar 

  7. Tostain J, Li G, Gentil-Perret A et al (2010) Carbonic anhydrase 9 in clear cell renal cell carcinoma: a marker for diagnosis, prognosis and treatment. Eur J Cancer 46:3141–3148

    Article  PubMed  CAS  Google Scholar 

  8. Liao SY, Aurelio ON, Jan K et al (1997) Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer Res 57:2827–2831

    PubMed  CAS  Google Scholar 

  9. Genega EM, Ghebremichael M, Najarian R et al (2010) Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type and grade. Am J Clin Pathol 134:873–879

    Article  PubMed  CAS  Google Scholar 

  10. Leppert JT, Lam JS, Pantuck AJ et al (2005) Carbonic anhydrase IX and the future of molecular markers in renal cell carcinoma. BJU Int 96:281–285

    Article  PubMed  CAS  Google Scholar 

  11. Al-Hamadie HA, Alden D, Qin LX et al (2008) Carbonic anhydrase IX expression in clear cell renal cell carcinoma: an immunohistochemical study comparing 2 antibodies. Am J Surg Pathol 32(3):377–382

    Article  Google Scholar 

  12. McNichols DW, Segura JW, DeWeerd JH (1981) Renal cell carcinoma: long-term survival and late recurrence. J Urol 126:17–23

    PubMed  CAS  Google Scholar 

  13. Janzen NK, Kim HL, Figlin RA et al (2003) Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 30:843–852

    Article  PubMed  Google Scholar 

  14. Bukowski RM (1997) Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2. Cancer 80:1198–1220

    Article  PubMed  CAS  Google Scholar 

  15. Motzer RJ, Bacik J, Mariani T et al (2002) Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology. J Clin Oncol 20:2376–2381

    Article  PubMed  Google Scholar 

  16. Winum JY, Scozzafava A, Montera JL et al (2009) Inhibition of carbonic anhydrase IX: a new strategy against cancer. Anticancer Agents Med Chem 9:693–702

    PubMed  CAS  Google Scholar 

  17. Li G, Passebosc-Faure K, Feng G et al (2007) MN/CA9: a potential gene marker for detection of malignant cells in effusions. Biomarkers 12(2):214–220

    Article  PubMed  CAS  Google Scholar 

  18. Ilie M, Mazure NM, Hofman V et al (2010) High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer. Br J Cancer 102:1627–1635

    Article  PubMed  CAS  Google Scholar 

  19. Travis WD, Brambilla E, Muller-Hermelink HK et al (2004) World Health Organization classification of tumors: pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC, Lyon

    Google Scholar 

  20. Choueiri TK, Regan MM, Rosenberg JE et al (2010) Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy. BJU Int 106:772–778

    Article  PubMed  CAS  Google Scholar 

  21. Bui MH, Seligson D, Han K et al (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. Clin Cancer Res 9:802–811

    PubMed  CAS  Google Scholar 

  22. Tickoo SK, Alden D, Olgac S (2007) Immunohistochemical expression of hypoxia inducible factor-1α and its downstream molecules in sarcomatoid renal cell carcinoma. J Urol 177:1258–1263

    Article  PubMed  CAS  Google Scholar 

  23. Kim SJ, Rabbani ZN, Vollmer RT (2004) Carbonic anhydrase IX in early-stage non-small cell lung cancer. Clin Cancer Res 10:7925–7933

    Article  PubMed  CAS  Google Scholar 

  24. Kim SJ, Rabbani ZN, Dewhirst MW (2005) Expression of HIF-1alpha, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer 49:325–335

    Article  PubMed  Google Scholar 

  25. Vermylen P, Roufosse C, Burny A (1999) Carbonic anhydrase IX antigen differentiates between preneoplastic malignant lesions in non-small cell lung carcinoma. Eur Respir J 14:806–811

    Article  PubMed  CAS  Google Scholar 

  26. Atkins M, Regan M, McDermott D (2005) Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11(10):3714–3721

    Article  PubMed  CAS  Google Scholar 

  27. Atkins MB, Choueiri TK, Cho D (2009) Treatment selection for patients with metastatic renal cell carcinoma. Cancer 115(10):2327–2333

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, The Ohio State University Medical Center, 410 W 10th Ave., E401 Doan Hall, Columbus, OH, 43210, USA

    Mitchell L. Ramsey, Benjamin J. Yuh & Debra L. Zynger

  2. Department of Urology, The Ohio State University Medical Center, Columbus, OH, 43210, USA

    Matthew T. Johnson

  3. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Anjana V. Yeldandi

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  1. Mitchell L. Ramsey
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  2. Benjamin J. Yuh
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  3. Matthew T. Johnson
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  4. Anjana V. Yeldandi
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  5. Debra L. Zynger
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Correspondence to Debra L. Zynger.

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Ramsey, M.L., Yuh, B.J., Johnson, M.T. et al. Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung. Virchows Arch 460, 89–93 (2012). https://doi.org/10.1007/s00428-011-1178-7

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  • DOI: https://doi.org/10.1007/s00428-011-1178-7

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