Skip to main content

Advertisement

Log in

High expression of MAGE-A10 cancer-testis antigen in triple-negative breast cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 31 January 2012

Abstract

Recent studies indicate that ER/PR/HER-2-negative (triple-negative, TN) breast cancers may be “CTA-rich” tumors, suggesting the possibility of CTA-based cancer vaccines as a treatment option for patients bearing these tumors. MAGE-A10 together with NY-ESO-1 is probably the most immunogenic CTA, representing a potentially highly attractive target of active specific immunotherapies. Paraffin-embedded tumor sections were collected retrospectively from 165 breast cancer patients diagnosed between 2002 and 2003. Immunohistochemical staining for MAGE-A10 and NY-ESO-1 was performed. The expression of MAGE-A10 and NY-ESO-1 was correlated with other clinicopathological variables. MAGE-A10 expression (score ≥ 2+) was detected in 105/164 (64%), and NY-ESO-1 expression (score ≥ 2+) was observed in 14/164 (8.5%) patients. No correlation between MAGE-A10 and NY-ESO-1 expression and tumor size, tumor grade, Ki-67 and lymph nodes status was detectable. MAGE-A10 expression was significantly associated with ER-negative (P = 0.002), PR-negative (P = 0.002) and HER-2-negative (P = 0.044) tumors. We clearly showed that MAGE-A10 is frequently expressed in the group of TN patients, where the majority (85.7%) of tumors express this CTA. Because of limited therapeutic options for the triple-negative breast cancer, the frequent expression of MAGE-A10 CTA in these cancers may offer the opportunity for a much needed additional treatment for this group of patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Simpson AJ, Caballero OL, Jungbluth A, et al. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005;5:615–25.

    Article  PubMed  CAS  Google Scholar 

  2. van Pel A, van der Bruggen P, Coulie PG, et al. Genes coding for tumour antigens recognized by cytolytic T lymphocytes. Immunol Rev. 1995;145:229–50.

    Article  PubMed  Google Scholar 

  3. Knuth A, Wolfel T, Klehmann E, Boon T, Meyer zum Buschenfelde KH. Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci USA. 1989;86:2804–8.

    Article  PubMed  CAS  Google Scholar 

  4. Traversari C, van der Bruggen P, Van den Eynde B, Hainaut P, Lemoine C, Ohta N, Old L, Boon T. Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T lymphocytes. Immunogenetics. 1992;35:145–52.

    Article  PubMed  CAS  Google Scholar 

  5. Chomez P, et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61:5544–51.

    PubMed  CAS  Google Scholar 

  6. Forslund OK, Nordquist K. The melanoma antigen genes: any clues to their functions in normal tissues? Exp Cell Res. 2001;265:185–94.

    Article  CAS  Google Scholar 

  7. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004;4:1.

    PubMed  Google Scholar 

  8. Sugita M, et al. Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res. 2002;62:3971–9.

    PubMed  CAS  Google Scholar 

  9. van der Bruggen P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991;254:1643–7.

    Article  PubMed  Google Scholar 

  10. Chen YT, Scanlan MJ, Sahin U, Tureci O, Gure AO, et al. A testicular antigen aberrantly expressed in human cancer detected by autologous antibody screening. Proc Natl Acad Sci USA. 1997;94:1914–8.

    Article  PubMed  CAS  Google Scholar 

  11. Jager E, Strockert E, Zidianakis Z, Chen YT, Karbach J, et al. Humoral immuno responses of cancer patients against “Cancer-Testis”antigen NY-ESO-1: correlation with clinical events. Int J Cancer. 1999;84:506–10.

    Article  PubMed  CAS  Google Scholar 

  12. Davis ID, Chen W, Jackson H, Parente P, Shackleton M, et al. Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4 (+) and CD8(+) T cell responses in humans. Proc Natl Acad Sci USA. 2004;101:10697–702.

    Article  PubMed  CAS  Google Scholar 

  13. Bricard G, Bouzourene H, Martinet O, Rimoldi D, Halkic N, Gilllet M, Chaubert P, Macdonald HR, Romero P, Cerottini JC, Speiser DE. Naturally acquired MAGE-A10 and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma. J Immunol. 2005;174:1709–16.

    PubMed  CAS  Google Scholar 

  14. Sartorius R, Pisu P, D’ Apice L, Pizzela L, Romano C, Cortese G, Giorgini A, Santoni A, Velotti F, De BP. The use of filamentous bacteriophage fd to deliver MAGE-A10 or MAGE-A3 HLA-A2- restricted peptides and to induce strong antitumor CTL responses. J Immunol. 2008;180:19–28.

    Google Scholar 

  15. Valmori D, Dutoit V, Rubio-Godoy V, Chambaz C, Lienard D, Guillaume P, Romero P, Cerottini JC, Rimoldi D. Frequent cytolytic T-cell responses to peptide MAGE-A10 (254–262) in melanoma. Cancer Res. 2001;61:509–12.

    PubMed  CAS  Google Scholar 

  16. World Health Organisation. World Health Organisation classification of tumors. In: Tavassoli FA, Devilee P, editors. Tumors of the breast and female genital organs. Lyon: IARC Press; 2003.

  17. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.

    Article  PubMed  CAS  Google Scholar 

  18. Taylor CR. The current role of immunohistochemistry in diagnostic pathology. Adv Pathol Lab Med. 1994;7:59–65.

    CAS  Google Scholar 

  19. Bartlett JMS, Going JJ, Mallon EA, et al. Evaluating HER2 amplification and overexpression in breast cancer. J Pathol. 2001;195:422–8.

    Article  PubMed  CAS  Google Scholar 

  20. Key G, Petersen JL, Becker MHG, et al. New antiserum against Ki-67 antigen suitable for double immunostaining of paraffin wax sections. J Clin Pathol. 1993;46:1080–4.

    Article  PubMed  CAS  Google Scholar 

  21. Schulthz-Thater E, Piscuoglio S, Lezzi G, Le Magnen C, Zajac P, Carafa V, Terracciano L, Tornillo L, Spagnoli C. MAGE-A10 is a nuclear protein frequently expressed in high percentage of tumor cells in lung, skin and urothelial malignancies. Int J Cancer. 2011;129:1137–48.

    Article  Google Scholar 

  22. Yoshida A, Abe H, Ohkuri T, Wakita D, Sato M, Noguchi D, Miyamoto M, Morikawa T, Kondo S, Ikeda H, Nishimura T. Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens and T cell infiltration in non small cell lung carcinoma and their prognostic significance. Int J Oncol. 2006;28:1089–98.

    PubMed  CAS  Google Scholar 

  23. Bolli M, Schultz-Thater E, Zajac P, Guller U, Feder C, Sanguedolce F, Carafa V, Terracciano L, Hudolin T, Spagnoli GC, Tornillo L. NY-ESO-1/LAGE-1 coexpression with MAGE-A cancer/testis antigens: a tissue microarray study. Int J Cancer. 2005;115:960–6.

    Article  PubMed  CAS  Google Scholar 

  24. Allred DC, Harvey JM, Berardo M, et al. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–68.

    PubMed  CAS  Google Scholar 

  25. Caballero OL, Chen YT. Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci. 2009;100:2014–21.

    Article  PubMed  CAS  Google Scholar 

  26. Rosenberg SA. Progress in human tumor immunology and immunotherapy. Nature. 2001;411:380–4.

    Article  PubMed  CAS  Google Scholar 

  27. Theurillat JP, Ingold F, Frei C, Zippelius A, Varga Z, et al. NY-ESO-1 protein expression in primary breast carcinoma and metastases: correlation with CD8 + T-cell and CD 79a + plasmacytic/B-cell infiltration. Int J Cancer. 2007;120:2411–7.

    Article  PubMed  CAS  Google Scholar 

  28. Bandic D, Juretic A, Sarcevic B, Separovic V, Kujundzic-Tisljak M, et al. Expression and possible prognostic role of MAGE-A4, NY-ESO-1 and HER-2 antigens in women with relapsing invasive ductal breast cancer: retrospective immunohistochemical study. Croat Med J. 2006;47:32–41.

    PubMed  CAS  Google Scholar 

  29. Kavalar R, Sarcevic B, Spagnoli GC, Separovic V, Samija M, Terracciano L, Heberer M, Juretic A. Expression of MAGE tumor-associated antigens is inversely correlated with tumor differentiation in invasive ductal breast cancers: an immunohistochemical study. Virchows Arch. 2001;439:127–31.

    Article  PubMed  CAS  Google Scholar 

  30. Curigliano G, Viale G, Ghioni M, Jungbluth AA, Bagnardi V, Spagnoli GC, Neville AM, Nolè F, Rotmensz N, Goldhirsch A. Cancer-testis antigen expression in triple-negative breast cancer. Ann Oncol. 2011;22:98–103.

    Article  PubMed  CAS  Google Scholar 

  31. Chen YT, Ross DS, Chiu R, Zhou XK, Chen YY, Lee P, Hoda SA, Simpso AJ, Old LJ, Caballero O, Neville AM. Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers. PLoS One. 2011;6(3):e17876.

    Article  PubMed  CAS  Google Scholar 

  32. Gure AO, et al. Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res. 2005;11:8055–62.

    Article  PubMed  CAS  Google Scholar 

  33. Velazquez EF, et al. Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM)–correlation with prognostic factors. Cancer Immun. 2007;7:11–7.

    PubMed  Google Scholar 

  34. Andrade VC, Vettore AL, Felix RS, Almeida MS, Carvalho F, Oliveira JS, Chauffaille ML, Andriolo A, Caballero OL, Zago MA, Colleoni GW. Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun. 2008;8:2.

    PubMed  Google Scholar 

  35. Napoletano C, Bellati F, Tarquini E, Tomao F, Taurino F, Spagnoli G, Rughetti A, Muzii L, Nuti M, Benedetti Panici P. MAGE-A and NY-ESO-1 expression in cervical cancer: prognostic factors and effects of chemotherapy. Am J Obstet Gynecol. 2008;198:91–7.

    Article  Google Scholar 

  36. Kurashige T, Noguchi Y, Saika T, et al. NY-ESO-1 expression and immunogenicity associated with transitional cell carcinoma: correlation with tumor grade. Cancer Res. 2001;61:4671–4.

    PubMed  CAS  Google Scholar 

  37. Brasseur F, Rimoldi D, Lienard D, et al. Expression of MAGE genes in primary and metastatic cutaneous melanoma. Int J Cancer. 1995;63:375–80.

    Article  PubMed  CAS  Google Scholar 

  38. Grigoriadis A, Caballero OL, Hoek KS, da Silva L, Chen YT, et al. CT-X antigen expression in human breast cancer. Proc Natl Acad Sci USA. 2009;106:13494–8.

    Article  Google Scholar 

  39. Atanackovic D, Altorki NK, Cao Y, Ritter E, Ferrara CA, Ritter G, Hoffman EW, Bokemeyer C, Old LJ, Gnjatic S. Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming. Proc Natl Acad Sci USA. 2008;105:1650–5.

    Article  PubMed  CAS  Google Scholar 

  40. Jäger E, Karbach J, Gnjatic S, Neumann A, Bender A, Valmori D, Ayyoub M, Ritter E, Ritter G, Jäger D, Panicali D, Hoffman E, Pan L, Oettgen H, Old LJ, Knuth A. Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. Proc Natl Acad Sci USA. 2006;103:14453–8.

    Article  PubMed  Google Scholar 

  41. van Baren N, Bonnet MC, Dréno B, Khammari A, Dorval T, Piperno-Neumann S, Liénard D, Speiser D, Marchand M, Brichard VG, Escudier B, Négrier S, Dietrich PY, Maraninchi D, Osanto S, Meyer RG, Ritter G, Moingeon P, Tartaglia J, van der Bruggen P, Coulie PG, Boon T. Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells. J Clin Oncol. 2005;23:9008–21.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Badovinac Črnjević Tanja.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanja, B.Č., Giulio, S., Antonio, J. et al. High expression of MAGE-A10 cancer-testis antigen in triple-negative breast cancer. Med Oncol 29, 1586–1591 (2012). https://doi.org/10.1007/s12032-011-0120-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-0120-9

Keywords

Navigation