This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liao, S.-Y. Articles by Stanbridge, E. J. Search for Related Content PubMed PubMed Citation Articles by Liao, S.-Y. Articles by Stanbridge, E. J.

Identification of the MN/CA9 Protein As a Reliable Diagnostic Biomarker of Clear Cell Carcinoma of the Kidney¹

Departments of Medicine [S-Y. L.] and Microbiology and Molecular Genetics [O. A. N., K. J., E. J. S.], University of California, Irvine, College of Medicine, Irvine, California 92697-4025; Department of Pathology, St. Joseph Hospital, Orange, California [S-Y. L.]; and Academy of Sciences of the Czech Republic, Institute of Virology, Prague, Czech Republic [J. Z.]

The MN/CA9 protein is a tumor-associated antigen that has been shown to have diagnostic utility in identifying cervical dysplasia and carcinoma. MN/CA9 expression is limited to very few normal tissues. We have now extended those observations to further investigate expression of the MN/CA9 protein in histological sections and fine-needle aspiration biopsy smears of normal kidney, benign renal cell lesions, all categories of renal cell carcinomas (clear/granular/spindle cell, chromophilic cell, chromophobic cell, and collecting duct cell RCCs), metastatic RCCs, and non-renal cell clear cell adenocarcinomas. We have found that high levels of MN/CA9 expression is seen in all primary RCCs, cystic RCCs, and metastatic RCCs, with the exception of two cases of the chromophobe cell type, which were MN/CA9 negative. Identical MN/CA9 immunostaining was also observed in the aspiration cytological smears. In contrast, all benign lesions, including pyelonephritis, renal cysts, adenomas, oncocytomas, and normal kidney, did not express the MN/CA9 protein. Thus, we conclude that MN/CA9 protein expression could serve as a valuable adjunct to the cytological and histological diagnosis of benign renal cysts versus cystic RCC, adenoma versus RCC, and oncocytoma versus granular cell RCC. Diffuse membraneous staining of all RCCs (with the exception of chromophobic cell RCC) suggests that MN/CA9 protein expression might have an important clinical utility in the early detection and treatment of RCC. Absence of MN/CA9 expression in non-renal cell clear cell adenocarcinoma also indicates that MN/CA9 protein expression may be used as a differential diagnostic biomarker of metastatic clear cell RCC.

¹ This study was supported in part by National Cancer Institute Grant CA19104 and the Clark Family Fund.

² To whom requests for reprints should be addressed, at University of California, Irvine, Department of Microbiology and Molecular Genetics, College of Medicine, 240 Medical Science I, Building B, Irvine, CA 92697-4025. Phone: (714) 824-7042; Fax: (714) 824-2454; E-mail: ejstanbr@uci.edu.

Received 4/25/97. Accepted 6/ 2/97.

This article has been cited by other articles:

				B. C. Leibovich, Y. Sheinin, C. M. Lohse, R. H. Thompson, J. C. Cheville, J. Zavada, and E. D. Kwon Carbonic Anhydrase IX Is Not an Independent Predictor of Outcome for Patients With Clear Cell Renal Cell Carcinoma J. Clin. Oncol., October 20, 2007; 25(30): 4757 - 4764. [Abstract] [Full Text] [PDF]

				J. A. Haapasalo, K. M. Nordfors, M. Hilvo, I. J. Rantala, Y. Soini, A.-K. Parkkila, S. Pastorekova, J. Pastorek, S. M. Parkkila, and H. K. Haapasalo Expression of Carbonic Anhydrase IX in Astrocytic Tumors Predicts Poor Prognosis Clin. Cancer Res., January 15, 2006; 12(2): 473 - 477. [Abstract] [Full Text] [PDF]

				M. A. Proescholdt, C. Mayer, M. Kubitza, T. Schubert, S.-Y. Liao, E. J. Stanbridge, S. Ivanov, E. H. Oldfield, A. Brawanski, and M. J. Merrill Expression of hypoxia-inducible carbonic anhydrases in brain tumors Neuro-oncol, October 1, 2005; 7(4): 465 - 475. [Abstract] [PDF]

				R. R. Raval, K. W. Lau, M. G. B. Tran, H. M. Sowter, S. J. Mandriota, J.-L. Li, C. W. Pugh, P. H. Maxwell, A. L. Harris, and P. J. Ratcliffe Contrasting Properties of Hypoxia-Inducible Factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-Associated Renal Cell Carcinoma Mol. Cell. Biol., July 1, 2005; 25(13): 5675 - 5686. [Abstract] [Full Text] [PDF]

				J. Hu and T. E. Spencer Carbonic Anhydrase Regulate Endometrial Gland Development in the Neonatal Uterus Biol Reprod, July 1, 2005; 73(1): 131 - 138. [Abstract] [Full Text] [PDF]

				M. Hilvo, M. Rafajova, S. Pastorekova, J. Pastorek, and S. Parkkila Expression of Carbonic Anhydrase IX in Mouse Tissues J. Histochem. Cytochem., October 1, 2004; 52(10): 1313 - 1322. [Abstract] [Full Text] [PDF]

				J. S. Lam, A. S. Belldegrun, and R. A. Figlin Tissue Array-Based Predictions of Pathobiology, Prognosis, and Response to Treatment for Renal Cell Carcinoma Therapy Clin. Cancer Res., September 15, 2004; 10(18): 6304S - 6309S. [Abstract] [Full Text] [PDF]

				K. Maseide, R. A. Kandel, R. S. Bell, C. N. Catton, B. O'Sullivan, J. S. Wunder, M. Pintilie, D. Hedley, and R. P. Hill Carbonic Anhydrase IX as a Marker for Poor Prognosis in Soft Tissue Sarcoma Clin. Cancer Res., July 1, 2004; 10(13): 4464 - 4471. [Abstract] [Full Text] [PDF]

				G. Li, M. Cuilleron, A. Gentil-Perret, M. Cottier, K. Passebosc-Faure, C. Lambert, C. Genin, and J. Tostain Rapid and Sensitive Detection of Messenger RNA Expression for Molecular Differential Diagnosis of Renal Cell Carcinoma Clin. Cancer Res., December 15, 2003; 9(17): 6441 - 6446. [Abstract] [Full Text] [PDF]

				A. Zisman, A. J. Pantuck, M. H. T. Bui, J. W. Said, R. R. Caliliw, N. Rao, P. Shintaku, F. Berger, S. S. Gambhir, and A. S. Belldegrun LABAZ1: A Metastatic Tumor Model for Renal Cell Carcinoma Expressing the Carbonic Anhydrase Type 9 Tumor Antigen Cancer Res., August 15, 2003; 63(16): 4952 - 4959. [Abstract] [Full Text] [PDF]

				D. E.B. Swinson, J. L. Jones, D. Richardson, C. Wykoff, H. Turley, J. Pastorek, N. Taub, A. L. Harris, and K. J. O'Byrne Carbonic Anhydrase IX Expression, a Novel Surrogate Marker of Tumor Hypoxia, Is Associated With a Poor Prognosis in Non-Small-Cell Lung Cancer J. Clin. Oncol., February 1, 2003; 21(3): 473 - 482. [Abstract] [Full Text] [PDF]

				M. H. T. Bui, D. Seligson, K.-r. Han, A. J. Pantuck, F. J. Dorey, Y. Huang, S. Horvath, B. C. Leibovich, S. Chopra, S.-Y. Liao, et al. Carbonic Anhydrase IX Is an Independent Predictor of Survival in Advanced Renal Clear Cell Carcinoma: Implications for Prognosis and Therapy Clin. Cancer Res., February 1, 2003; 9(2): 802 - 811. [Abstract] [Full Text] [PDF]

				M. I. Koukourakis, A. Giatromanolaki, E. Sivridis, K. Simopoulos, J. Pastorek, C. C. Wykoff, K. C. Gatter, and A. L. Harris Hypoxia-regulated Carbonic Anhydrase-9 (CA9) Relates to Poor Vascularization and Resistance of Squamous Cell Head and Neck Cancer to Chemoradiotherapy Clin. Cancer Res., November 1, 2001; 7(11): 3399 - 3403. [Abstract] [Full Text] [PDF]

				S. K. Chia, C. C. Wykoff, P. H. Watson, C. Han, R. D. Leek, J. Pastorek, K. C. Gatter, P. Ratcliffe, and A. L. Harris Prognostic Significance of a Novel Hypoxia-Regulated Marker, Carbonic Anhydrase IX, in Invasive Breast Carcinoma J. Clin. Oncol., August 15, 2001; 19(16): 3660 - 3668. [Abstract] [Full Text] [PDF]

				N. J. P. Beasley, C. C. Wykoff, P. H. Watson, R. Leek, H. Turley, K. Gatter, J. Pastorek, G. J. Cox, P. Ratcliffe, and A. L. Harris Carbonic Anhydrase IX, an Endogenous Hypoxia Marker, Expression in Head and Neck Squamous Cell Carcinoma and its Relationship to Hypoxia, Necrosis, and Microvessel Density Cancer Res., July 1, 2001; 61(13): 5262 - 5267. [Abstract] [Full Text] [PDF]

				S. A. KARUMANCHI, L. JIANG, B. KNEBELMANN, A. K. STUART-TILLEY, S. L. ALPER, and V. P. SUKHATME VHL tumor suppressor regulates Cl-/HCO3- exchange and Na+/H+ exchange activities in renal carcinoma cells Physiol Genomics, April 2, 2001; 5(3): 119 - 128. [Abstract] [Full Text] [PDF]

				S. Ivanov, S.-Y. Liao, A. Ivanova, A. Danilkovitch-Miagkova, N. Tarasova, G. Weirich, M. J. Merrill, M. A. Proescholdt, E. H. Oldfield, J. Lee, et al. Expression of Hypoxia-Inducible Cell-Surface Transmembrane Carbonic Anhydrases in Human Cancer Am. J. Pathol., March 1, 2001; 158(3): 905 - 919. [Abstract] [Full Text] [PDF]

				C. C. Wykoff, N. Beasley, P. H. Watson, L. Campo, S. K. Chia, R. English, J. Pastorek, W. S. Sly, P. Ratcliffe, and A. L. Harris Expression of the Hypoxia-Inducible and Tumor-Associated Carbonic Anhydrases in Ductal Carcinoma in Situ of the Breast Am. J. Pathol., March 1, 2001; 158(3): 1011 - 1019. [Abstract] [Full Text] [PDF]

				G. Li, K. Passebosc-Faure, C. Lambert, A. Gentil-Perret, F. Blanc, E. Oosterwijk, J.-F. Mosnier, C. Genin, and J. Tostain The Expression of G250/MN/CA9 Antigen by Flow Cytometry: Its Possible Implication for Detection of Micrometastatic Renal Cancer Cells Clin. Cancer Res., January 1, 2001; 7(1): 89 - 92. [Abstract] [Full Text]

				C. C. Wykoff, N. J. P. Beasley, P. H. Watson, K. J. Turner, J. Pastorek, A. Sibtain, G. D. Wilson, H. Turley, K. L. Talks, P. H. Maxwell, et al. Hypoxia-inducible Expression of Tumor-associated Carbonic Anhydrases Cancer Res., December 1, 2000; 60(24): 7075 - 7083. [Abstract] [Full Text]

				C. F. Eisenberger, M. Schoenberg, C. Enger, S. Hortopan, S. Shah, N.-H. Chow, F. F. Marshall, and D. Sidransky Diagnosis of Renal Cancer by Molecular Urinalysis J Natl Cancer Inst, December 1, 1999; 91(23): 2028 - 2032. [Abstract] [Full Text] [PDF]

				S. Kaluz, M. Kaluzova, R. Opavsky, S. Pastorekova, A. Gibadulinova, F. Dequiedt, R. Kettmann, and J. Pastorek Transcriptional Regulation of the MN/CA 9 Gene Coding for the Tumor-associated Carbonic Anhydrase IX. IDENTIFICATION AND CHARACTERIZATION OF A PROXIMAL SILENCER ELEMENT J. Biol. Chem., November 12, 1999; 274(46): 32588 - 32595. [Abstract] [Full Text] [PDF]

				S. V. Ivanov, I. Kuzmin, M.-H. Wei, S. Pack, L. Geil, B. E. Johnson, E. J. Stanbridge, and M. I. Lerman Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes PNAS, October 13, 1998; 95(21): 12596 - 12601. [Abstract] [Full Text] [PDF]