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.
Similar content being viewed by others
References
Simpson AJ, Caballero OL, Jungbluth A, et al. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005;5:615–25.
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.
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.
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.
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.
Forslund OK, Nordquist K. The melanoma antigen genes: any clues to their functions in normal tissues? Exp Cell Res. 2001;265:185–94.
Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004;4:1.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Taylor CR. The current role of immunohistochemistry in diagnostic pathology. Adv Pathol Lab Med. 1994;7:59–65.
Bartlett JMS, Going JJ, Mallon EA, et al. Evaluating HER2 amplification and overexpression in breast cancer. J Pathol. 2001;195:422–8.
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.
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.
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.
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.
Allred DC, Harvey JM, Berardo M, et al. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–68.
Caballero OL, Chen YT. Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci. 2009;100:2014–21.
Rosenberg SA. Progress in human tumor immunology and immunotherapy. Nature. 2001;411:380–4.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-011-0120-9