Abstract
To determine if ovarian cancer patients would be suitable for MAGE-peptide vaccine-based immunotherapy, the frequency of expression of the MAGE-1-4 genes in ovarian tumours was assessed using reverse transcription polymerase chain reaction (RT-PCR) and product verification with digoxigenin-labelled oligonucleotide probes specific for each MAGE gene. In addition, the frequency of expression of more recently discovered tumour antigens (BAGE, GAGE -1, -2 and GAGE -3, -6) was established using RT-PCR and ethidium bromide staining. In this study 1/16 normal ovarian tissue specimens and 11/25 benign lesions expressed MAGE-1. In non-malignant tissue there was preferential expression of MAGE-1 in premenopausal women. A total of 15/27 malignant specimens expressed MAGE-1, including 10/14 serous cystadenocarcinomas. Expression of other tumour antigens was infrequent. The finding of MAGE-1 expression in both benign and malignant tissue questions previous assumptions regarding the role of MAGE genes in carcinogenesis. In addition, preferential MAGE-1 gene expression in non-malignant premenopausal tissue suggests that the MAGE genes may be involved in cellular proliferation as opposed to carcinogenesis or possibly that MAGE gene expression is under cyclical hormonal control. Finally, this study indicates that serous cystadenocarcinomas may be suitable tumours for MAGE-1 peptide immunotherapy.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boël P., Wildmann C., Sensi M. L., Brasseur R., Renauld J. C., Coulie P., Boon T., van der Bruggen P. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity. 1995 Feb;2(2):167–175. doi: 10.1016/s1074-7613(95)80053-0. [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]
- 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]
- Finke J., Fritzen R., Ternes P., Lange W., Dölken G. An improved strategy and a useful housekeeping gene for RNA analysis from formalin-fixed, paraffin-embedded tissues by PCR. Biotechniques. 1993 Mar;14(3):448–453. [PubMed] [Google Scholar]
- Gaugler B., Van den Eynde B., van der Bruggen P., Romero P., Gaforio J. J., De Plaen E., Lethé B., Brasseur F., Boon T. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med. 1994 Mar 1;179(3):921–930. doi: 10.1084/jem.179.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hacker N. F., Berek J. S., Lagasse L. D., Nieberg R. K., Elashoff R. M. Primary cytoreductive surgery for epithelial ovarian cancer. Obstet Gynecol. 1983 Apr;61(4):413–420. [PubMed] [Google Scholar]
- Hulka B. S. Cancer screening. Degrees of proof and practical application. Cancer. 1988 Oct 15;62(8 Suppl):1776–1780. doi: 10.1002/1097-0142(19881015)62:1+<1776::aid-cncr2820621314>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- Inoue H., Li J., Honda M., Nakashima H., Shibuta K., Arinaga S., Ueo H., Mori M., Akiyoshi T. MAGE-1 mRNA expression in gastric carcinoma. Int J Cancer. 1995 Feb 20;64(1):76–77. doi: 10.1002/ijc.2910640115. [DOI] [PubMed] [Google Scholar]
- Mori M., Inoue H., Mimori K., Shibuta K., Baba K., Nakashima H., Haraguchi M., Tsuji K., Ueo H., Barnard G. F. Expression of MAGE genes in human colorectal carcinoma. Ann Surg. 1996 Aug;224(2):183–188. doi: 10.1097/00000658-199608000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mulcahy K. A., Rimoldi D., Brasseur F., Rodgers S., Liénard D., Marchand M., Rennie I. G., Murray A. K., McIntyre C. A., Platts K. E. Infrequent expression of the MAGE gene family in uveal melanomas. Int J Cancer. 1996 Jun 11;66(6):738–742. doi: 10.1002/(SICI)1097-0215(19960611)66:6<738::AID-IJC5>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
- Patard J. J., Brasseur F., Gil-Diez S., Radvanyi F., Marchand M., François P., Abi-Aad A., Van Cangh P., Abbou C. C., Chopin D. Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder. Int J Cancer. 1995 Feb 20;64(1):60–64. doi: 10.1002/ijc.2910640112. [DOI] [PubMed] [Google Scholar]
- Russo V., Dalerba P., Ricci A., Bonazzi C., Leone B. E., Mangioni C., Allavena P., Bordignon C., Traversari C. MAGE BAGE and GAGE genes expression in fresh epithelial ovarian carcinomas. Int J Cancer. 1996 Jul 29;67(3):457–460. doi: 10.1002/(SICI)1097-0215(19960729)67:3<457::AID-IJC24>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
- Shichijo S., Yamada A., Sagawa K., Iwamoto O., Sakata M., Nagai K., Itoh K. Induction of MAGE genes in lymphoid cells by the demethylating agent 5-aza-2'-deoxycytidine. Jpn J Cancer Res. 1996 Jul;87(7):751–756. doi: 10.1111/j.1349-7006.1996.tb00288.x. [DOI] [PMC free article] [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., Luescher I. F., Lurquin C., Chomez P., Van Pel A., De Plaen E., Amar-Costesec A., Boon T. A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med. 1992 Nov 1;176(5):1453–1457. doi: 10.1084/jem.176.5.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van den Eynde B., Peeters O., De Backer O., Gaugler B., Lucas S., Boon T. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med. 1995 Sep 1;182(3):689–698. doi: 10.1084/jem.182.3.689. [DOI] [PMC free article] [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]
- Yamada A., Kataoka A., Shichijo S., Kamura T., Imai Y., Nishida T., Itoh K. Expression of MAGE-1, MAGE-2, MAGE-3/-6 and MAGE-4a/-4b genes in ovarian tumors. Int J Cancer. 1995 Dec 20;64(6):388–393. doi: 10.1002/ijc.2910640607. [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]
- van der Burg M. E., van Lent M., Buyse M., Kobierska A., Colombo N., Favalli G., Lacave A. J., Nardi M., Renard J., Pecorelli S. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med. 1995 Mar 9;332(10):629–634. doi: 10.1056/NEJM199503093321002. [DOI] [PubMed] [Google Scholar]

