Medical Oncology

, Volume 29, Issue 3, pp 1586–1591 | Cite as

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

  • Badovinac Črnjević TanjaEmail author
  • Spagnoli Giulio
  • Juretić Antonio
  • Jakić-Razumović Jasminka
  • Podolski Paula
  • Šarić Nera
Original Paper


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.


Breast cancer MAGE-A10 NY-ESO-1 Cancer-testis antigens 


Conflict of interest



  1. 1.
    Simpson AJ, Caballero OL, Jungbluth A, et al. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005;5:615–25.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 6.
    Forslund OK, Nordquist K. The melanoma antigen genes: any clues to their functions in normal tissues? Exp Cell Res. 2001;265:185–94.CrossRefGoogle Scholar
  7. 7.
    Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004;4:1.PubMedGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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. 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.PubMedGoogle Scholar
  16. 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.Google Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Taylor CR. The current role of immunohistochemistry in diagnostic pathology. Adv Pathol Lab Med. 1994;7:59–65.Google Scholar
  19. 19.
    Bartlett JMS, Going JJ, Mallon EA, et al. Evaluating HER2 amplification and overexpression in breast cancer. J Pathol. 2001;195:422–8.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedGoogle Scholar
  25. 25.
    Caballero OL, Chen YT. Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci. 2009;100:2014–21.PubMedCrossRefGoogle Scholar
  26. 26.
    Rosenberg SA. Progress in human tumor immunology and immunotherapy. Nature. 2001;411:380–4.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.PubMedGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.CrossRefGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.CrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Badovinac Črnjević Tanja
    • 1
    Email author
  • Spagnoli Giulio
    • 3
  • Juretić Antonio
    • 1
  • Jakić-Razumović Jasminka
    • 2
  • Podolski Paula
    • 1
  • Šarić Nera
    • 1
  1. 1.Oncology DepartmentUniversity Hospital ZagrebZagrebCroatia
  2. 2.Pathology DepartmentUniversity Hospital ZagrebZagrebCroatia
  3. 3.Institute of Research and Hospital ManagementUniversity of BaselBaselSwitzerland

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