Abstract
Cancer/testis (CT) antigens such as those encoded by the MAGE-gene family are expressed in a wide variety of malignant neoplasms. In normal tissues, expression is generally restricted to testis. Current knowledge of the expression pattern of CT antigens is mainly based on mRNA analysis. Little is known about actual protein expression. We previously developed MA454, a monoclonal antibody (mAb) to MAGE-1 recombinant protein. By employing antigen retrieval techniques, we show that MA454 is reactive on formalin-fixed paraffin-embedded tissues. Immunohistochemical (IHC) analysis of a normal tissue panel revealed staining solely in germ cells of testes. A series of 59 lung tumours was co-typed for MAGE-1 expression by RT–PCR and by immunohistochemistry with MA454. MA454 was positive in 19/59 cases (32%). MAGE-1 mRNA was found in 17 of the 54 cases (32%) available for RT–PCR. Of the 19 MA454-reactive tumours, 15 showed a highly heterogeneous pattern of expression. The other 4 MA454 positive cases revealed immunoreactivity in >25% of tumour areas. Of the 53 cases typed for both, mRNA and protein expression, 48 co-typed whereas 5 cases were discrepant, a likely consequence of heterogeneous MAGE-1 expression. The predominantly focal expression of MAGE-1 suggests that this antigen might not be sufficient as a sole target for immunotherapeutic approaches. © 2000 Cancer Research Campaign
Keywords: MAGE-1 antigen, monoclonal antibody MA454
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- Amar-Costesec A., Godelaine D., Stockert E., van der Bruggen P., Beaufay H., Chen Y. T. The tumor protein MAGE-1 is located in the cytosol of human melanoma cells. Biochem Biophys Res Commun. 1994 Oct 28;204(2):710–715. doi: 10.1006/bbrc.1994.2517. [DOI] [PubMed] [Google Scholar]
- Boon T, Old LJ. Cancer Tumor antigens. Curr Opin Immunol. 1997 Oct 1;9(5):681–683. doi: 10.1016/s0952-7915(97)80049-0. [DOI] [PubMed] [Google Scholar]
- Brasseur F., Marchand M., Vanwijck R., Hérin M., Lethé B., Chomez P., Boon T. Human gene MAGE-1, which codes for a tumor-rejection antigen, is expressed by some breast tumors. Int J Cancer. 1992 Nov 11;52(5):839–841. doi: 10.1002/ijc.2910520528. [DOI] [PubMed] [Google Scholar]
- Carrel S., Schreyer M., Spagnoli G., Cerottini J. C., Rimoldi D. Monoclonal antibodies against recombinant-MAGE-1 protein identify a cross-reacting 72-kDa antigen which is co-expressed with MAGE-1 protein in melanoma cells. Int J Cancer. 1996 Jul 29;67(3):417–422. doi: 10.1002/(SICI)1097-0215(19960729)67:3<417::AID-IJC17>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
- Chen Y. T., Stockert E., Chen Y., Garin-Chesa P., Rettig W. J., van der Bruggen P., Boon T., Old L. J. Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1004–1008. doi: 10.1073/pnas.91.3.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheville J. C., Roche P. C. MAGE-1 and MAGE-3 tumor rejection antigens in human germ cell tumors. Mod Pathol. 1999 Oct;12(10):974–978. [PubMed] [Google Scholar]
- De Plaen E., Arden K., Traversari C., Gaforio J. J., Szikora J. P., De Smet C., Brasseur F., van der Bruggen P., Lethé B., Lurquin C. Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics. 1994;40(5):360–369. doi: 10.1007/BF01246677. [DOI] [PubMed] [Google Scholar]
- De Smet C., De Backer O., Faraoni I., Lurquin C., Brasseur F., Boon T. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7149–7153. doi: 10.1073/pnas.93.14.7149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferlazzo G., Meta M., Mesiti M., Cangemi G., Iemmo R., Quartarone G., Fecarotta E., Semino C., Pietra G., Melioli G. Detection of MAGE-1, -2, and -3 messenger RNA in tissue samples derived from lung and mammary tumors. Ann N Y Acad Sci. 1996 Apr 30;784:448–452. doi: 10.1111/j.1749-6632.1996.tb16261.x. [DOI] [PubMed] [Google Scholar]
- Fischer C., Gudat F., Stulz P., Noppen C., Schaefer C., Zajac P., Trutmann M., Kocher T., Zuber M., Harder F. High expression of MAGE-3 protein in squamous-cell lung carcinoma. Int J Cancer. 1997 Jun 11;71(6):1119–1121. doi: 10.1002/(sici)1097-0215(19970611)71:6<1119::aid-ijc34>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
- Gudat F., Zuber M., Dürmüller U., Kocher T., Schaefer C., Noppen C., Spagnoli G. The tumour-associated antigen MAGE-1 is detectable in formalin-fixed paraffin sections of malignant melanoma. Virchows Arch. 1996 Oct;429(2-3):77–81. doi: 10.1007/BF00192428. [DOI] [PubMed] [Google Scholar]
- Hofbauer G. F., Schaefer C., Noppen C., Böni R., Kamarashev J., Nestle F. O., Spagnoli G. C., Dummer R. MAGE-3 immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution. Am J Pathol. 1997 Dec;151(6):1549–1553. [PMC free article] [PubMed] [Google Scholar]
- Itoh K., Hayashi A., Nakao M., Hoshino T., Seki N., Shichijo S. Human tumor rejection antigens MAGE. J Biochem. 1996 Mar;119(3):385–390. doi: 10.1093/oxfordjournals.jbchem.a021252. [DOI] [PubMed] [Google Scholar]
- Jungbluth A. A., Busam K. J., Kolb D., Iversen K., Coplan K., Chen Y. T., Spagnoli G. C., Old L. J. Expression of MAGE-antigens in normal tissues and cancer. Int J Cancer. 2000 Feb 15;85(4):460–465. [PubMed] [Google Scholar]
- Jurk M., Kremmer E., Schwarz U., Förster R., Winnacker E. L. MAGE-11 protein is highly conserved in higher organisms and located predominantly in the nucleus. Int J Cancer. 1998 Mar 2;75(5):762–766. doi: 10.1002/(sici)1097-0215(19980302)75:5<762::aid-ijc16>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
- Kocher T., Schultz-Thater E., Gudat F., Schaefer C., Casorati G., Juretic A., Willimann T., Harder F., Heberer M., Spagnoli G. C. Identification and intracellular location of MAGE-3 gene product. Cancer Res. 1995 Jun 1;55(11):2236–2239. [PubMed] [Google Scholar]
- Lucas S., De Smet C., Arden K. C., Viars C. S., Lethé B., Lurquin C., Boon T. Identification of a new MAGE gene with tumor-specific expression by representational difference analysis. Cancer Res. 1998 Feb 15;58(4):743–752. [PubMed] [Google Scholar]
- Lurquin C., De Smet C., Brasseur F., Muscatelli F., Martelange V., De Plaen E., Brasseur R., Monaco A. P., Boon T. Two members of the human MAGEB gene family located in Xp21.3 are expressed in tumors of various histological origins. Genomics. 1997 Dec 15;46(3):397–408. doi: 10.1006/geno.1997.5052. [DOI] [PubMed] [Google Scholar]
- Old L. J., Chen Y. T. New paths in human cancer serology. J Exp Med. 1998 Apr 20;187(8):1163–1167. doi: 10.1084/jem.187.8.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rimoldi D., Salvi S., Reed D., Coulie P., Jongeneel V. C., De Plaen E., Brasseur F., Rodriguez A. M., Boon T., Cerottini J. C. cDNA and protein characterization of human MAGE-10. Int J Cancer. 1999 Sep 9;82(6):901–907. doi: 10.1002/(sici)1097-0215(19990909)82:6<901::aid-ijc21>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- Sahin U., Türeci O., Pfreundschuh M. Serological identification of human tumor antigens. Curr Opin Immunol. 1997 Oct;9(5):709–716. doi: 10.1016/s0952-7915(97)80053-2. [DOI] [PubMed] [Google Scholar]
- Sakata M. Expression of MAGE gene family in lung cancers. Kurume Med J. 1996;43(1):55–61. doi: 10.2739/kurumemedj.43.55. [DOI] [PubMed] [Google Scholar]
- Schultz-Thater E., Juretic A., Dellabona P., Lüscher U., Siegrist W., Harder F., Heberer M., Zuber M., Spagnoli G. C. MAGE-1 gene product is a cytoplasmic protein. Int J Cancer. 1994 Nov 1;59(3):435–439. doi: 10.1002/ijc.2910590324. [DOI] [PubMed] [Google Scholar]
- Takahashi K., Shichijo S., Noguchi M., Hirohata M., Itoh K. Identification of MAGE-1 and MAGE-4 proteins in spermatogonia and primary spermatocytes of testis. Cancer Res. 1995 Aug 15;55(16):3478–3482. [PubMed] [Google Scholar]
- 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(3):145–152. doi: 10.1007/BF00185107. [DOI] [PubMed] [Google Scholar]
- Van den Eynde B. J., Boon T. Tumor antigens recognized by T lymphocytes. Int J Clin Lab Res. 1997;27(2):81–86. doi: 10.1007/BF02912440. [DOI] [PubMed] [Google Scholar]
- Van den Eynde B. J., van der Bruggen P. T cell defined tumor antigens. Curr Opin Immunol. 1997 Oct;9(5):684–693. doi: 10.1016/s0952-7915(97)80050-7. [DOI] [PubMed] [Google Scholar]
- Weynants P., Lethé B., Brasseur F., Marchand M., Boon T. Expression of mage genes by non-small-cell lung carcinomas. Int J Cancer. 1994 Mar 15;56(6):826–829. doi: 10.1002/ijc.2910560612. [DOI] [PubMed] [Google Scholar]
- Zuber M., Spagnoli G. C., Kocher T., Lüscher U., Schaefer C., Noppen C., Gudat F., Harder F., Heberer M. Heterogeneity of melanoma antigen-1 (MAGE-1) gene and protein expression in malignant melanoma. Eur Surg Res. 1997;29(5):403–410. doi: 10.1159/000129550. [DOI] [PubMed] [Google Scholar]
- van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen E., Van den Eynde B., Knuth A., Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643–1647. doi: 10.1126/science.1840703. [DOI] [PubMed] [Google Scholar]
