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Expression of cancer testis antigens in human BRCA-associated breast cancers: potential targets for immunoprevention?

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Abstract

Introduction

Novel breast cancer risk-reducing strategies for individuals with germline mutations of the BRCA1 and/or BRCA2 genes are urgently needed. Identification of antigenic targets that are expressed in early cancers, but absent in normal breast epithelium of these high-risk individuals, could provide the basis for the development of effective immunoprophylactic strategies. Cancer testis (CT) antigens are potential candidates because their expression is restricted to tumors, and accumulating data suggest that they play important roles in cellular proliferation, stem cell function, and carcinogenesis. The objective of this study was to examine the expression of CT antigens and their frequency in BRCA-associated breast cancers.

Methods

Archived breast cancer tissues (n = 26) as well as morphologically normal breast tissues (n = 7) from women carrying deleterious BRCA 1 and/or 2 mutations were obtained for antigen expression analysis by immunohistochemistry. Expression of the following CT antigens was examined: MAGE-A1, MAGE-A3, MAGE-A4, MAGE-C1.CT7, NY-ESO-1, MAGE-C2/CT10, and GAGE.

Results

CT antigens were expressed in 16/26 (61.5%, 95% CI 43–80%) of BRCA-associated cancers, including in situ tumors. Thirteen of twenty-six (50%) breast cancers expressed two or more CT antigens; three cancers expressed all seven CT antigens. MAGE-A was expressed in 13/26 (50%) of cancers, NY-ESO-1 was expressed in 10/26 (38%) of tumors. In contrast, none of the CT antigens were expressed in adjacent or contralateral normal breast epithelium (P = 0.003).

Conclusions

We report a high CT antigen expression rate in BRCA-associated breast cancer as well as the lack of expression of these antigens in benign breast tissue of carriers, identifying CT antigens as potential vaccine targets for breast cancer prevention in these high-risk individuals.

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Acknowledgments

The authors wish to thank Nelli Ziguridis at the NYUCI Tissue Bank for specimen acquisition and Dr. Franco Muggia for his critical review of the manuscript. Sylvia Adams was supported in part by NCI K23 CA125205, and the NYU Cancer Institute Core facilities were supported by NIH 5P30CA016087-27.

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Authors and Affiliations

  1. New York University Cancer Institute, New York University School of Medicine, 462 First Avenue, Bellevue C&D556, New York, NY, 10016, USA

    Sylvia Adams, Luba Greeder, Elsa Reich, Yongzhao Shao, Baljit Singh & Sandra Demaria

  2. Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Denise Fosina, Nicole Hanson, Jodie Tassello & Achim A. Jungbluth

  3. Institute of Surgical Research and Hospital Management, University Hospital Basel, Basel, Switzerland

    Giulio C. Spagnoli

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  1. Sylvia Adams
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  2. Luba Greeder
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  3. Elsa Reich
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Correspondence to Sylvia Adams.

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Adams, S., Greeder, L., Reich, E. et al. Expression of cancer testis antigens in human BRCA-associated breast cancers: potential targets for immunoprevention?. Cancer Immunol Immunother 60, 999–1007 (2011). https://doi.org/10.1007/s00262-011-1005-7

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  • DOI: https://doi.org/10.1007/s00262-011-1005-7

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