Abstract
The monoclonal antibody G250 (mAbG250) raised against a human renal cell carcinoma (RCC) has been shown to react with a large number of RCCs. Recently, G250 antigen was isolated and found to be homologous to the MN/CA9 gene originally identified in HeLa cells. To determine whether G250 antigen (MN/CA IX/G250) could be a potential therapeutic target and a tumour marker, a total of 147 cases of RCC were investigated immunohistochemically as well as by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, total RNAs extracted from patients’ peripheral blood samples were analysed for MN/CA9/G250 mRNA signals. Immunohistochemistry demonstrated strong expression in 128/147 (87.1%) of RCCs, in contrast to the lack of expression observed in normal tissues. RT-PCR analyses of frozen specimens resulted in the clear detection of MN/CA9/G250 mRNA signals in 137/147 (93.2%), and despite subtle differences the results were almost identical to those for immunohistochemistry. Although high-grade and -stage tumours exhibited significantly lower expression than low-grade and -stage tumours, a large proportion of tumours expressed MN/G250 protein as well as mRNA. RT-PCR analysis of patients’ blood samples revealed the presence of circulating MN/CA9/G250 expressing cells. These findings suggest that this antigen may be a potential therapeutic target as well as diagnostic marker for RCCs.
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16 November 2011
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References
Allhoff, EP, Liedke, S, Kirchner, H, Atzpodien, J, De Riese, W, Stief, CG & Jonas, U (1991) Current clinical relevance of immunotherapy in metastatic renal cancer. World J Urol 9: 228–231
Brewer, C, Liao, SY, Wilczynski, SP, Pastrekova, S, Pastorek, J, Zavada, J, Kurozaki, T, Manetta, A, Berman, ML, DiSaia, PJ & Stanbridge, EJ (1996) A study of biomarkers in cervical carcinoma and clinical correlation of the novel biomarker MN. Gynecol Oncol 63: 337–344
De Riese, W, Allhoff, EP, Kirchner, H, Stief, CG, Atzpodien, J, Maschek, H & Jonas, U (1991) Complete spontaneous regression in metastatic renal cell carcinoma – an update and review. World J Urol 9: 184–191
Hamdy, FC, Lawry, J, Anderson, JB, Parsons, MA, Rees, RC & Williams, JL (1992) Circulating prostate specific antigen-positive cells correlate with metastatic prostate cancer. Brit J Cancer 69: 392–396
Ignatoff, JM, Oefelein, MG, Watkin, W, Chmiel, JS & Kaul, KL (1997) Prostate specific antigen reverse transcriptase-polymerase chain reaction assay in preoperative staging of prostate cancer. J Urol 158: 1870–1875
Ivanov, SV, Kuzmin, I, Wei, MH, Pack, S, Geil, L, Johnson, BE, Stanbridge, EJ & Lerman, MI (1998) Down-regulation of transmembrane carbonic anhydrases in renal call carcinoma cell lines by wild-type von Hippel-Lindau transgenes. Proc Natl Acad Sci USA 95: 12596–12601
McKiernan, JM, Buttyan, R, Bander, NH, Stifelman, MD, Katz, AE, Chen, MW, Olsson, CA & Sawczuk, IS (1997) Expression of the tumor-associated gene MN: a potential biomarker for human renal cell carcinoma. Cancer Res 57: 2362–2365
McKiernan, JM, Stifelman, MD, Emanuel, ER, Katz, AE, Bander, NH, Olsson, CA, Buttyan, R & Sawczuk, IS (1998) The molecular detection of renal cancer cells via a peripheral blood assay. J Urol Suppl 159: 170
Liao, SY, Brewer, C, Zavada, J, Pastorek, J, Pastreková, S, Manetta, A, Berman, ML, DiSaia, PJ & Stanbridge, EJ (1994) Identification of the MN antigen as a diagnostic biomarker of cervical intraepithelial squamous and glandular neoplasia and cervical carcinomas. Am J Pathol 145: 598–609
Liao, SY, Aurelio, ON, Jan, K, Zavada, J & Stanbridge, EJ (1997) Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer Res 57: 2827–2831
Oosterwijk, E, Ruiter, DJ, Hoedemaeker, JC, Huiskens-V, JW, Meij, D, Jonas, U, Fleuren, GJ, Zwartendijk, J, Hoedemaeker, PJ & Warnaar, SO (1986) Immunohistochemical analysis of monoclonal antibodies to renal antigens. Am J Pathol 123: 301–309
Oosterwijk, E, Bander, NH, Divgi, CR, Wakka, JC, Finn, RD, Carswell, EA, Larson, SM, Warnaar, SO, Fleuren, GJ, Oettgen, HF & Old, L (1993) Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. J Clin Oncol 11: 738–750
Oosterwijk, E, De Weijert, M, Van Bokhoven, A, Brakenhoff, RH, Peelen, WP & Debruyne, FMJ (1996) Molecular characterization of the renal cell carcinoma-associated antigen G250. Proc Amer Assoc Cancer Res 37: 461
Opavsky, R, Pastoreková, S, ZelnĂk, V, Gibadulinová, A, Stanbridge, EJ, Závada, J, Kettmann, R & Pastorek, J (1996) Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. Genomics 33: 480–487
Pastorek, J, Pastoreková, S, Callebaut, I, Mornon, JP, ZelnĂk, V, Opavsky, R, Zat’ovicová, M, Liao, S, Portetelle, D, Stanbridge, EJ, Závada, J, Burny, A & Kettmann, R (1994) Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. Oncogene 9: 2877–2888
Pastoreková, S, Závadoá, Z, Kostál, M, BabusĂková, O & Závada, J (1992) A novel quasi-viral agent, TaTu is a two-component system. Virology 187: 22–28
Pastoreková, S, Parkkila, S, Parkkila, AK, Opavsky, R, ZelnĂk, V, Saarnio, J & Pastorek, J (1997) Carbonic anhydrase IX, MN/CA IX: analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts. Gastroenterology 112: 398–408
Ritchie, AWS & deKernion, JB (1987) The natural history and clinical features of renal carcinoma. Semin Nephrol 7: 131–139
Saarnio, J, Parkkila, S, Parkkila, AK, Haukipuro, K, Pastoreková, S, Pastorek, J, Kairaluoma, MI & Karttunen, TJ (1997) Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/CA IX, with potential value as a marker of cell proliferation. Am J Pathol 153: 279–285
Sokoloff, MH, Tso, C-L, Kaboo, R, Nelson, S, Ko, J, Dorey, F, Figlin, RA, Pang, S, DeKernion, J & Belldegrun, A (1996) Quantitative polymerase chain reaction does not improve preoperative prostate cancer staging: a clinicopathological molecular analysis of 121 patients. J Urol 156: 1560–1566
Steffens, MG, Boerman, OC, Oosterwijk-Wakka, JC, Oosterhof, GO, Witjes, JA, Koenders, EB, Oyen, WJ, Buijd, WC, Debruyne, FMJ, Corstens, FH & Oosterwijk, E (1997) Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250. J Clin Oncol 15: 1529–1537
Tuner, JR, Odze, RD, Crum, FCP & Resnick, MB (1997) MN antigen expression in normal, preneoplastic, and neoplastic esophagus: a clinicopathological study of a new cancer-associated biomarker. Human Pathol 28: 740–744
Uemura, H, Okajima, E, Debruyne, FMJ & Oosterwijk, E (1994a) Internal image antidiotype antibodies related to renal cell carcinoma-associated antigen G250. Int J Cancer 56: 609–614
Uemura, H, Beniers, AMJC, Okajima, E, Debruyne, FMJ & Oosterwijk, E (1994b) Vaccination with anti-idiotype antibodies mimicking a renal cell carcinoma-associated antigen induces tumor immunity. Int J Cancer 58: 555–561
Uemura, H, Okajima, E, Debruyne, FMJ & Oosterwijk, E (1995) Anti-tumor effects induced by vaccination with anti-idiotype antibodies in 7 mice with established human renal cell carcinoma xenografts. Urol Oncol 1: 73–79
Uemura, H, Kitagawa, H, Hirao, Y, Okajima, E, Debruyne, FMJ & Oosterwijk, E (1997) Expression of tumor-associated antigen MN/G250 in urologic carcinoma: potential therapeutic target. J Urol Suppl 157: 377
Van Dijk, J, Uemura, H, Beniers, AMJC, Peelen, WP, Zegveld, STh, Fleuren, GJ, Warnaar, SO & Oosterwijk, E (1994) Therapeutic effects of monoclonal antibody G250, interferons and tumor necrosis factor, in mice with renal cell carcinoma xenografts. Int J Cancer 56: 262–268
Wirth, MP (1993) Immunotherapy for metastatic renal cell carcinoma. Urol Clin N Am 20: 283–295
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Uemura, H., Nakagawa, Y., Yoshida, K. et al. MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas. Br J Cancer 81, 741–746 (1999). https://doi.org/10.1038/sj.bjc.6690757
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DOI: https://doi.org/10.1038/sj.bjc.6690757
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