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Expression of MAGE-C1/CT7 and selected cancer/testis antigens in ovarian borderline tumours and primary and recurrent ovarian carcinomas

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Abstract

MAGE-C1/CT7, NY-ESO-1, GAGE and MAGE-A4 are members of the cancer/testis (CT) antigen family, which have been proposed as potential targets for cancer immunotherapy. To determine the prevalence and biologic relevance of the novel CT antigen MAGE-C1/CT7 and other antigens, 36 ovarian borderline tumours (BTs), 230 primary ovarian carcinomas (OCs) and 80 recurrent OCs were immunohistochemically analysed using the monoclonal antibodies CT7-33 (MAGE-C1/CT7), E978 (NY-ESO-1), clone 26 (GAGE) and 57B (MAGE-A4). Positivity of at least one CT antigen was present in 39.5 % (81/205) of primary OC and in 50 % (26/52) of all recurrences. Expression of the novel CT antigen MAGE-C1/CT7 was most commonly seen with positivity in 24.5 % of primary and 35.1 % of recurrent OC. MAGE-A4, GAGE and NY-ESO-1 expressions were seen in 22.7, 13.9 and 7.1 % of primary and 22.6, 17.5 and 8.9 % of recurrent OC, respectively. Analysis of histological subtypes (serous, endometrioid, clear cell, mucinous and transitional) exhibited variable expression with negativity in all mucinous OC. High-grade serous OC revealed CT antigen expression in 5.6 to 28 % with MAGE-C1/CT7 being the most frequent, but without correlation with stage or overall survival. MAGE-C1/CT7 expression and coexpression of CT antigens were significantly correlated with grade of endometrioid OC. None of the BT showed CT antigen expression. No significant correlation was seen with stage, overall survival or response to chemotherapy. In summary, CT antigens are expressed in a certain subset of OC with no expression in BT or OC of mucinous histology. These findings may have implications for the design of polyvalent vaccination strategies for ovarian carcinomas.

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Acknowledgments

The authors thank Martina Storz and Silvia Behnke for their excellent technical assistance. This work was supported by the Cancer Research Institute and the Zurich Cancer League (Zurich).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics statement

The project was approved by the local ethics review boards of Bale and Zurich (Kantonale Ethikkomission Zurich, StV 27–2009). The aim of this retrospective study was immunohistochemical analysis of tumour tissue of patients with ovarian neoplasias (carinomas and borderline tumours). We tried to find a tissue marker that gives evidence for biologic behaviour (prognostic marker, good/bad prognosis) or can possibly be used as therapeutic targets for immunotherapies (therapeutic markers).

All tissue samples were taken from the archives after diagnostic processes were completed. Samples (186) were retrieved from the archives of the Institute for Surgical Pathology, University Hospital Zurich, Switzerland, covering the period from 1995 to 2005. Tissue samples of further 80 patients were available from the Institutes of Pathology, University Hospital Bale, Cantonal Hospital St. Gallen, Cantonal Hospital Baden and Cantonal Hospital Liestal from the period between 1985 and 2003.

According to the ethical rules of our local ethics committee, patient data were pseudoanonymised with patient identification numbers. To our knowledge, the results of this study have no influence on patient’s treatment (yet). However, should our results be of importance for the therapy of individual patients, they can again be identified.

In agreement with the local ethics committee, informed consent of individual patients was not obtained. Most patients of the collective examined are already dead. Thus, we relinquished to get patient consent or consent of family members in order not to upset them.

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Authors and Affiliations

  1. Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland

    Anne-Katrin Zimmermann, Holger Moch & Rosmarie Caduff

  2. Institute of Pharmaceutical Science, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093, Zurich, Switzerland

    Jochen Imig

  3. Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital, August-Forel-Str. 7, 8032, Zurich, Switzerland

    Agnes Klar

  4. Onkozentrum Hirslanden Zürich, Klinik Hirslanden, Witellikerstrasse 40, Zurich, 8032, Switzerland

    Christoph Renner

  5. Institute of Social and Preventive Medicine, University of Zurich, Vogelsangstrasse 10, 8091, Zurich, Switzerland

    Dimitri Korol

  6. Department of Gynecology, University Hospital Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland

    Daniel Fink

  7. Institute of Pathology, Kantonsspital Baden AG, 5404, Baden, AG, Switzerland

    Sylvia Stadlmann & Gad Singer

  8. Clinic of Oncology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Alexander Knuth

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  1. Anne-Katrin Zimmermann
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  2. Jochen Imig
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  3. Agnes Klar
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  7. Sylvia Stadlmann
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  11. Rosmarie Caduff
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Correspondence to Anne-Katrin Zimmermann.

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Zimmermann, AK., Imig, J., Klar, A. et al. Expression of MAGE-C1/CT7 and selected cancer/testis antigens in ovarian borderline tumours and primary and recurrent ovarian carcinomas. Virchows Arch 462, 565–574 (2013). https://doi.org/10.1007/s00428-013-1395-3

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  • DOI: https://doi.org/10.1007/s00428-013-1395-3

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