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Expression of the membrane complement regulatory protein CD59 (protectin) is associated with reduced survival in colorectal cancer patients

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Abstract

It has been known for some time that the immune system can recognise growing tumours, and that tumours may respond by modulation of molecules, which make them resistant to further attack. Expression, over-expression, or loss of these molecules may function as markers of tumour progression and prognosis. Among such molecules are the membrane-bound complement regulatory proteins (mCRP), which protect cells from bystander attack by autologous complement. These include CD59 (protectin), which prevents formation of the MAC complex in the terminal stages of complement activation. In the present study, we evaluated immunohistochemical expression of CD59 in a series of over 460 well-characterised colorectal cancers using tissue microarrays (TMA), and related this information to known tumour and patient variables and to survival. The CD59 expression was observed in 69 (15%) of cases overall, and was significantly associated with tumour grade. In contrast, no associations were noted with tumour site, stage or histological type. On survival analysis, a further correlation was observed between expression of CD59 by the colorectal tumours and a reduction in disease-specific patient survival. This observation was strongest for patients with early stage disease. However, a negative impact on survival was also seen in those patients with late stage disease. These results indicate that TMA linked to good clinicopathological databases with good long term follow up are useful tools for determining new prognostic indicators that can be used in future patient management. Immune surveillance may result in immune–editing that induces variable expression of a range of target antigens, and these may be useful prognostic markers. This study has identified CD59 expression as a marker of poor prognosis in colorectal cancer patients.

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References

  1. Bjorge L, Jensen TS, Matre R (1996) Characterisation of the complement-regulatory proteins decay accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46) on a human colonic adenocarcinoma cell line. Cancer Immunol Immunother 42:185–192

    Article  PubMed  CAS  Google Scholar 

  2. Bjorge L, Vedeler CA, Ulvestad E, Matre R (1994) Expression and function of CD59 on colonic adenocarcinoma cells. Eur J Immunol 24:1597–1603

    Article  PubMed  CAS  Google Scholar 

  3. Camp RL, Charette LA, Rimm DL (2000) Validation of tissue microarray technology in breast carcinoma. Lab Invest 80:1943–1949

    PubMed  CAS  Google Scholar 

  4. Donin N, Jurianz K, Ziporen L, Schultz S, Kirschfink M, Fishelson Z (2003) Complement resistance of human cells depends on membrane regulatory proteins, protein kinases and sialic acid. Clin Exp Immunol 131:254–263

    Article  PubMed  CAS  Google Scholar 

  5. Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Ann Rev Immunol 22:329–360

    Article  CAS  Google Scholar 

  6. Durrant LG, Chapman MA, Buckley DJ, Spendlove I, Robins RA, Armitage NC (2003) Enhanced expression of the complement regulatory protein CD55 predicts a poor prognosis in colorectal cancer patients. Cancer Immunol Immunother 52:638–642

    Article  PubMed  CAS  Google Scholar 

  7. Fishelson Z, Donin N, Zell S, Schultz S, Kirschfink M (2003) Obstacles to cancer immunotherapy: expression of membrane complement regulatory proteins (mCRPs) in tumors. Mol Immunol 40:109–123

    Article  PubMed  CAS  Google Scholar 

  8. Gelderman KA, Kuppen PJ, Bruin W, Fleuren GJ, Gorter A (2002) Enhancement of the complement activating capacity of 17-1A mAb to overcome the effect of membrane-bound complement regulatory proteins on colorectal carcinoma. Eur J Immunol 32:128–135

    Article  PubMed  CAS  Google Scholar 

  9. Gelderman KA, Tomlinson S, Ross GD, Gorter A (2004) Complement function in mAb-mediated cancer immunotherapy. Trends Immunol 25:158–164

    Article  PubMed  CAS  Google Scholar 

  10. Gorter A, Meri S (1999) Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today 20:576–582

    Article  PubMed  CAS  Google Scholar 

  11. Hosch SB, Scheunemann P, Luth M, Inndorf S, Stoecklein NH, Erbersdobler A, Rehders A, Gundlach M, Knoefel WT, Izbicki JR (2001) Expression of 17-1A antigen and complement resistance factors CD55 and CD59 on liver metastases in colorectal cancer. J Gastrointest Surg 5:673–679

    Article  PubMed  CAS  Google Scholar 

  12. Inoue T, Mizuno M, Uesu T, Ueki T, Tsuji T (1994) Distribution of complement regulatory proteins, decay-accelerating factor, CD59/homologous restriction factor 20 and membrane cofactor protein in human colorectal adenoma and cancer. Acta Med Okayama 48:271–277

    PubMed  CAS  Google Scholar 

  13. Inoue T, Yamakawa M, Takakhashi T (2002) Expresssion of complement regulating factors in gastric cancer cells. J Clin Pathol Mol Pathol 55:193–199

    CAS  Google Scholar 

  14. Juhl H, Helmig F, Baltzer K, Kalthoff H, Henne-Bruns D, Kremer B (1997) Frequent expression of complement resistance factors CD46, CD55, and CD59 on gastrointestinal cancer cells limits the therapeutic potential of monoclonal antibody 17-1A. J Surg Oncol 64:222–230

    Article  PubMed  CAS  Google Scholar 

  15. Jurianz K, Maslak S, Garcia-Schuler H, Fishelson Z, Kirschfink M (1999) Neutralization of complement regulatory proteins augments lysis of breast carcinoma cells targeted with rhumAb anti-HER2. Immunopharmacology 42:209–218

    Article  PubMed  CAS  Google Scholar 

  16. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high throughput molecular profiling of tumour specimens. Nat Med 4:844–847

    Article  PubMed  CAS  Google Scholar 

  17. Koretz K, Bruderlein S, Henne C, Moller P (1993) Expression of CD59, a complement regulator protein and a second ligand of the CD2 molecule, and CD46 in normal and neoplastic colorectal epithelium. Br J Cancer 68:926–931

    PubMed  CAS  Google Scholar 

  18. Lachmann PJ (1991) The control of homologous lysis. Immunol Today 12:312–315

    Article  PubMed  CAS  Google Scholar 

  19. Madjd Z, Durrant LG, Bradley R, Spendlove I, Ellis IO, Pinder SE (2004) Loss of CD55 is associated with aggressive breast tumors. Clin Cancer Res 10:2797–2803

    Article  PubMed  CAS  Google Scholar 

  20. Madjd Z, Durrant LG, Pinder SE, Ellis IO, Ronan J, Lewis S, Rushmere NK, Spendlove I (2005) Do poor-prognosis breast tumors express membrane cofactor proteins (CD46)? Cancer Immunol Immunother 54:149–156

    Article  PubMed  CAS  Google Scholar 

  21. Madjd Z, Pinder SE, Paish C, Ellis IO, Carmichael J, Durrant LG (2003) Loss of CD59 expression in breast tumors correlates with poor survival. J Pathol 200:633–639

    Article  PubMed  CAS  Google Scholar 

  22. Madjd Z, Spendlove I, Pinder SE, Ellis IO, Durrant LG (2005) Total loss of MHC class I is an independent indicator of good prognosis in breast cancer. Int J Cancer (e-pub ahead of print)

  23. Maio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, Visintin A, Altomonte M, Fonsatti E (1998) Structure, distribution, and functional role of protectin (CD59) in complement-suceptibility and in immunotherapy of human malignancies. Int J Oncol 13:305–318

    PubMed  CAS  Google Scholar 

  24. Meri S, Waldmann H, Lanchman PJ (1991) Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissue. Lab Invest 65:532–537

    PubMed  CAS  Google Scholar 

  25. Muller-Eberhard HJ (1986) The membrane attack complex of complement. Ann Rev Immunol 4:503–528

    Article  CAS  Google Scholar 

  26. National Institute for Clinical Excellence (2004) Improving outcomes in colorectal cancers: manual update. NICE, London

  27. Niehans GA, Cherwitz DL, Staley NA, Knapp DJ, Dalmasso AP (1996) Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay accelerating factor), and CD59 (protectin). Am J Pathol 149:129–142

    PubMed  CAS  Google Scholar 

  28. Quinn M, Babb P, Brock A, Kirby L, Jones J (2001) Cancer trends in England and Wales 1950–1999. The stationary office, London

    Google Scholar 

  29. Schmitt CA, Schwaeble W, Wittig BM, Meyer zum Buschenfelde KH, Dippold WG (1999) Expression and regulation by interferon-γ of the membrane-bound complement regulators CD46 (MCP), CD55 (DAF) and CD59 in gastrointestinal tumors. Eur J Cancer 35:117–124

    Article  PubMed  CAS  Google Scholar 

  30. Thorsteinsson L, O‘Dowd G, Harrington PM, Johnson PM (1998) The complement regulatory proteins CD46 and CD59 but not CD55, are highly expressed by glandular epithelium of human breast and colorectal tumor tissues. APMIS 106:869–878

    PubMed  CAS  Google Scholar 

  31. Torhorst J, Bucher C, Kononen J, Hass P, Zuber M, Kochli OR, Mross F, Dieterich H, Moch H, Mihatsch M, Kallioniemi OP, Sauter G (2001) Tissue microarrays for the rapid linking of molecular changes to clinical endpoints. Am J Pathol 159:2249–2256

    PubMed  CAS  Google Scholar 

  32. Xu C, Jung M, Burkhardt M, Stephan C, Schnorr D, Loening S, Jung K, Dietel M, Kristiansen G (2005) Increased CD59 protein expression predicts a PSA relapse in patients after radical prostatectomy. Prostate 62:224–232

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Mr John Ronan for technical assistance.

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Correspondence to Lindy G. Durrant.

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This article is a symposium paper from the "Robert Baldwin Symposium: 50 years of Cancer Immunotherapy", held in Nottingham, Great Britain, on 30th June 2005.

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Watson, N.F.S., Durrant, L.G., Madjd, Z. et al. Expression of the membrane complement regulatory protein CD59 (protectin) is associated with reduced survival in colorectal cancer patients. Cancer Immunol Immunother 55, 973–980 (2006). https://doi.org/10.1007/s00262-005-0055-0

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  • DOI: https://doi.org/10.1007/s00262-005-0055-0

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