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Carbonic anhydrase IX (CA IX) expression in renal cell carcinoma and transitional cell carcinoma of urinary tract


Authors: Lubomír Hyršl 1;  Jan Závada 2;  Zuzana Závadová 2;  Ivan Kawaciuk 3;  Štěpán Veselý 3;  Petr Škapa 4
Authors place of work: Urologické oddělení ON Kladno 1;  Ústav organické chemie a biochemie AV ČR, Praha 2;  Urologická klinika 2. LF UK a FNM, Praha 3;  Klinika patologie a molekulární medicíny 2. LF UK a FNM, Praha 4
Published in the journal: Ces Urol 2011; 15(2): 85-92
Category: Original article

Summary

Aim:
The aim of our study was to investigate the presence of soluble CA IX protein (s-CA IX) in tumor culture media in vitro and body fluids of patients carrying CA IX protein positive tumors. The final purpose was to improve present diagnostic methods to s-CA IX detection and to determine its possible use as a marker of renal clear cell carcinoma (RCC) and transitional cell carcinoma (TCC).

Material and methods:
In the preliminary study were two groups of patients: 1. RCC patients, 2. TCC patients. In the first group were included 31 RCC patients and 61 controles, in the second group 32 patients with endoscopic suspicion for TCC and 16 controles. We used immunohistochemical staining employing MAb M75 for CA IX identification in tumor tissue. In tumor extracts and body fluids we used Western blotting and ELISA for quantitation of the s-CA IX protein.

Results:
In the RCC group s-CA IX protein was detected only in patients with proven RCC. In the blood 13 (41,9%) from 31 were positive. In urine 19 (70%) from 27 were CA IX protein positive. Control specimens were all s-CA IX negative. In the TCC group the tumor was identified in 23 patients histologically. Positive s-CA IX was in 16 (69,6 %) of them. Negative finding of s-CA IX was in 7 (30,4%) patients. Serum from all TCC patients was s-CA IX negative, even the serum from patients with CA IX positive urine.

Conclusion:
We demonstrated shedding of CA IX into body fluids in patients with RCC and TCC, although in exremely low concentrations. Nevertheless, Western blotting combined with enhanced chemiluminiscence is specific and extremely sensitive method allowing s-CA IX detection in body fluids. Our present data suggest that suitable quantitave method for s-CA IX detection should be developed, which in turn will enable evaluation of clinical significance of CA IX expression in RCC and TCC patients.

Key words:
carbonic anhydrase IX, renal cell carcinoma, transitional cell carcinoma of urinary tract.


Zdroje

1. Pastorekova S, Parkkila S, Parkkila AK, et al. Carbonic anhydrase IX, MN/CA IX: Analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts. Gastroenterology 1997; 112: 398–408.

2. Saarnio J, Parkkila S, Parkkila AK, et al. Immunochemistry of carbonic anhydrase isozyme IX (MN/CA IX) in human gut reveals polarized expression in the epithelial cells with the highest proliferative capacity. J Histochem Cytochem 1998a; 46: 497–504.

3. Kivela AJ, Parkkila S, Saarnio J, et al. Expression of transmembrane carbonic anhydrase isoenzymes IX and XII in normal human pancreas and pancreatic tumours. Histochem Cell Biol 2000; 114: 197–204.

4. Karhumaa P, Kaunisto K, Parkkila S, et al. Expression of the transmembrane carbonic anhydrases, CA IX and CA XII, in the human male excurrent ducts. Mol Hum Reprod 2001; 7: 611–616.

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

6. Liao SY, Brewer C, Zavada J, et al. Identification of MN antigen as a diagnostic biomarker of cervical intraepithelial sqamous and glandular neoplasia and cervical carcinomas. Am J Pathol 1994; 145: 598–609.

7. Liao SY, Stanbridge EJ. Expression of MN/CA9 protein in Papanicolaou smears containing atypical glandular cells of undetermined significance is a diagnostic biomarker of cervical dysplasia and neoplasia. Cancer 2000; 88(5): 1108–1121.

8. Liao SY, Aurelio ON, Jan K, Zavada J, Stanbridge EJ. Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer Res 1997; 57: 2827–2831.

9. Oosterwijk E, Ruiter DJ, Hoedemaeker PJ, et al. Monoclonal antibody G250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney. Int J Cancer 1986; 38: 489–494.

10. Oosterwijk E, Debruyne FM. Radiolabeled monoclonal antibody G250 in renal-cell carcinoma. World J Urol 1995; 13: 186–190.

11. Uemura H, Kitagawa H, Hirao Y, et al. Expression of tumor-associated antigen MN/G250 in urologic carcinoma: Potential therapeutic target. J Urol 1997; 157(Suppl): 377.

12. McKiernan JM, Buttyan R, Bander NH, et al. Expression of the tumor-associated gene MN: A potential biomarker for human renal cell carcinoma. Cancer Res 1997; 57: 2362–2365.

13. Turner JR, Odze RD, Crum CP, Resnick MB. MN antigen expression in normal, preneoplastic, and neoplastic esophagus: A clinicopathological study of a new cancerassociated biomarker. Hum Pathol 1997; 28: 740–744.

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

15. Bartosova M, Parkkila S, Pohlodek K, et al. Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of cerbB2. J Pathol 2002; 197: 314–321.

16. Ortova-Gut M, Parkkila S, Vernerova Z, et al. Gastric hypeplasia in mice with targeted disruption of the carbonic anhydrase gene Car9. Gastroenteloogy 2002; 123: 1889–1903.

17. Zavada J, Zavadova Z, Pastorek J, et al. Human tumour-associated cell adhesion protein MN/ CA IX: identification of M75 epitope and of the region mediating cell adhesion. Brit J Cancer 2000; 82: 808–1813.

18. de la Taille A, Katz A, Cao Y, et al. Blood-based RT-PCR assays of MN/CA9 or PSMA: Clinical application in renal cancer patients. Urology 2000; 56: 393–398.

19. Zatovicova M, Tarabkova K, Svastova E, et al. Monoclonal antibodies generated in CA IXdeficient mice recognize different domains of tumor-associated hypoxia induced carbonic anhydrase IX. J Immunol Methods 2003; 282: 117–134.

20. Pastorekova S, Zavadilova Z, Kostal M, et al. A novel quasi-viral agent, MaTu, is a two-component system. Virology 1992; 187: 620–626.

21. Opavský R, Pastoreková S, Zelník V, et al. Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. Genomics 1996; 33: 480–487.

22. Turner KJ, Crew JP, Wykoff CC, et al. The hypoxiainducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer. Brit J Cancer 2002; 86: 1276–1282.

23. Pastorekova S, Zavada J. Carbonic anhydrase (CA IX) as a potential target for cancer therapy. Review article. Cancer Ther 2004; 2: 245–262.

24. Pastorekova S, Parkkila S, Zavada J. Tumor associated carbonic anhydrases and their clinical significance. Adv Clin Chem 2006; 42: 167–216.

25. Loncaster JA, Harris AL, Davidson SE, et al. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: Correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res 2001; 61: 6394–6399.

26. Harris AL. Hypoxia – a key regulatory factor in tumour growth. Nature Reviews Cancer 2002; 2: 38–47.

27. Zavada J, Zavadova Z, Pastorek J, et al. Human tumour-associated cell adhesion protein MN/ CA IX: Identification of M75 epitope and of the region mediating cell adhesion. Brit J Cancer 2000; 82: 808–1813.

28. Zavadova Z, Zavada J. Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment. Oncol Reports 2005; 13: 977–982.

Štítky
Paediatric urologist Nephrology Urology
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