DOI QR코드

DOI QR Code

A comprehensive Analysis of a Large Panel of Cancer/Testis (CT) Antigens in Korea Breast Cancer

한국 유방암 환자에서 cancer/testis antigen의 발현분석

  • Bae, Jae-Ho (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Kim, Min-Ju (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Park, Hae-Rim (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Song, Myung-Ha (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Kim, Jee-Yeon (pathology) ;
  • Lee, Chang-Hun (pathology) ;
  • Kwak, Hi-Suk (Surgery) ;
  • Lee, Sang-Yull (Departments of Biochemistry School of Medicine, Pusan National University)
  • 배재호 (부산대학교 의학전문대학원 생화학교실) ;
  • 김민주 (부산대학교 의학전문대학원 생화학교실) ;
  • 박해림 (부산대학교 의학전문대학원 생화학교실) ;
  • 송명하 (부산대학교 의학전문대학원 생화학교실) ;
  • 김지연 (병리학교실) ;
  • 이창훈 (병리학교실) ;
  • 곽희숙 (외과학교실) ;
  • 이상률 (부산대학교 의학전문대학원 생화학교실)
  • Published : 2009.07.30

Abstract

Cancer/testis (CT) antigens are immunogenic in cancer patients, exhibit highly tissue-restricted expression, and are considered promising target molecules for cancer vaccines. We investigated the expression of 13 CT genes in 29 Korean patients with primary breast carcinoma. The most frequently expressed CT genes were MAGE-3 (66%) and MAGE-1 (57%), followed by LAGE-1 (55%), NY-SAR-35 (49%), MAGE-4 (41%), NY-ESO-1 (38%), CT-7 (24%) and SSX-4 (24%), whereas SSX-1, SSX-2, MAGE-10 and NY-TLU-57 were found to be expressed significantly less often (3-7%) and SCP-l not all. Expression of at least one antigen was observed in 28 breast cancer samples. Immunohistochemistry was performed for NY-ESO-l and MAGE-3 protein expression in breast tumor samples. NY-ESO-l and MAGE-3 proteins were expressed in 11 of 29 (38%) and 12 of 29 (41 %) breast tumors. Our results suggest that CT antigens may be potential candidates for polyvalent immunotherapy in Korean breast cancer patients.

References

  1. Boel, P. C., M. L. Wildmann, R. Sensi, J. C. Brasseur, P. Renauld, T. Boon, and B. P. van der. 1995. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2, 167-175 https://doi.org/10.1016/S1074-7613(95)80053-0
  2. Chen, Q., H. Jackson, P. Parente, T. Luke, M. Rizkalla, T. Y. Tai, H. C. Zhu, N. A. Mifsud, N. Dimopoulos, K. A. Masterman, W. Hopkins, H. Goldie, E. Maraskovsky, S. Green, L. Miloradovic, J. McCluskey, L. J. Old, I. D. Davis, J. Cebon, and W. Chen. 2004. Immunodominant $CD4^{+}$ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant. Proc. Natl Acad. Sci. USA 101, 9363-9368 https://doi.org/10.1073/pnas.0403271101
  3. Greenlee, R. T., T. Murray, S. Bolden, and P. A. Wingo. 2000. Cancer statistics. CA Cancer J. Clin. 50, 7-33 https://doi.org/10.3322/canjclin.50.1.7
  4. Lee, S. Y. 2007. SEREX; discovery of tumor antigens. J. Life Science 17, 841-846 https://doi.org/10.5352/JLS.2007.17.6.841
  5. Lee, S. Y. , B. Williamson, O. L. Caballero, Y. T. Chen, M. J. Scanlan, G. Ritter, C. V. Jongeneel, A. J. Simpson, and L. J. Old. 2004. Identification of the gonad-specific anion transporter SLCO6A1 as a cancer/testis (CT) antigen expressed in human lung cancer. Cancer Immun. 17, 4-13
  6. Lee, S. Y., Y. Obata, M. Yoshida, E. Stockert, B. Williamson, A. Jungbluth, Y. T. Chen, L. J. Old, and M. J. Scanlan. 2003. Immunomic analysis of human sarcoma. Proc. Natl. Acad. Sci. USA 100, 2651-2656 https://doi.org/10.1073/pnas.0437972100
  7. Marchandab, M., C.J.A. Puntc, S. Aamdald, B. Escudiere, W.H.J. Kruitf, U. Keilholzg, L. Håkanssonh, N. van Barenab, Y. Humbletb, P. Muldersc, M.-F. Avrile, A. M. M. Eggermontf, C. Scheibenbogeng, J. Uitersi, J. Wandersi, M. Delirej, T. Boona, and G. Stoterf. 2003. Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur. J. Cancer 39, 70-77 https://doi.org/10.1016/S0959-8049(02)00479-3
  8. Mashino, K. N., F. Sadanaga, H. Tanaka, H. Yamaguchi, H. Nagashima, I. K. Sugimachi, and M. Mori. 2001. Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas. Br. J. Cancer 85, 713-720 https://doi.org/10.1054/bjoc.2001.1974
  9. Mischo, A., B. Kubuschok, K. Ertan, K. D. Preuss, B. Romeike, E. Regitz, C. Schormann,D. Bruijn, A. Wadle, F. Neumann, W. Schmidt, C. Renner, and M. Pfreundschuh. 2006. Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer. Intl. J. Cancer 118, 696-703 https://doi.org/10.1002/ijc.21352
  10. Rentzsch, C., S. Kayser, S. Stumm, I. Watermann, S. Walter, S. Stevanovic, D. Wallwiener, and B. Guckel. 2003. Evaluation of pre-existent immunity in patients with primary breast cancer: molecular and cellular assays to quantify antigen-specific T lymphocytes in peripheral blood mononuclear cells. Clin. Cancer Res. 9, 4376-4386
  11. Rimoldi, D., V. Rubio-Godoy, V. Dutoit, D. Lienard, S. Salvi, P. Guillaume, D. Speiser, E. Stockert, G. Spagnoli, C. Servis, J. C. Cerottini, F. Lejeune, P. Romero, and D. Valmori. 2000. Efficient simultaneous presentation of NY-ESO-1/LAGE-1 primary and nonprimary open reading frame-derived CTL epitopes in melanoma. J. Immunol. 165, 7253-7261 https://doi.org/10.4049/jimmunol.165.12.7253
  12. Russo, V., C. Traversari, A. Verrecchia, M. Mottolese, P. G. Natali, and C. Bordignon. 1995. Expression of the MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy. Int. J. Cancer 64, 216-221 https://doi.org/10.1002/ijc.2910640313
  13. Scanlan, M. J., A. J. Simpson, and L. J. Old. 2004. The cancer/ testis genes: review, standardization, and commentary. Cancer Immun. 4, 1
  14. Seregni, E., A. Coli, and N. Mazzucca. 2004. Circulating tumour markers in breast cancer. Eur. J. Nucl. Med. Mol. Imaging 31 (Suppl 1), 15-22 https://doi.org/10.1007/s00259-004-1523-z
  15. Simpson, A. J., O. L. Caballero, A. Jungbluth, Y. T. Chen, and L. J. Old. 2005. Cancer/testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 5, 615-625 https://doi.org/10.1038/nrc1669
  16. Slamon, D. J., B. Leyland-Jones, S. Shak, H. Fuchs, V. Paton, A. Bajamonde, T. Fleming, W. Eiermann, J. Wolte , M., Pegram, J. Baselga, and L. Norton. 2001. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783-792 https://doi.org/10.1056/NEJM200103153441101
  17. Van den Eynde, B., O. Peeters, O. De Backer, B. Gaugler, S. Lucas, and T. Boon. 1995. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J. Exp. Med. 182, 689-698 https://doi.org/10.1084/jem.182.3.689
  18. van der Bruggen, P., C. Traversari, P. Chomez, C. Lurquin, E. De Plaen, E. B. Van den, A. Knuth, and T. Boon. 1991. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254, 1643-1647 https://doi.org/10.1126/science.1840703
  19. Vaughan, H. A., S. Svobodova, D. SMacgregor D, S. Sturrock , A. A. Jungbluth, J. Browning, I. D. Davis, P. Parente, Y. T. Chen, E. Stockert, F. St Clair, L. J. Old, and J. Cebon. 2004. Immunohistochemical and molecular analysis of human melanomas for expression of the human cancer- testis antigens NY-ESO-1 and LAGE-1. Clin. Cancer Res. 10, 8396-8404 https://doi.org/10.1158/1078-0432.CCR-04-0809