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Amplification of the prolactin receptor gene in mammary lobular neoplasia

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Abstract

The identification of lobular carcinoma in situ (LCIS) in a patient’s specimen confers an appreciable increased risk of development of future invasive mammary carcinoma. However, the study of LCIS presents a challenge as it is usually only recognized in fixed specimens. Recent advances in high throughput genomics have made possible comprehensive copy number analysis of lesions such as this. Using array comparative genomic hybridization (aCGH), we characterized eight cases of lobular carcinoma (four invasive and four non-invasive) from microdissected samples of archival specimens and validated our results by quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) was performed on an independent set of 80 in situ ductal (DCIS) and lobular breast lesions to confirm our results. Amplification of the prolactin receptor gene (PRLr) was identified in 4/4 cases of LCIS by aCGH. We confirmed this amplification by qRT-PCR and demonstrated PRLr expression in 29/40 (73%) cases of lobular neoplasia by IHC. Amplification of PRLr was neither detected in 10 cases of DCIS nor in 5 areas of normal breast tissue by qRT-PCR and only 14/40 (35%) cases of DCIS showed PRLr expression by IHC (P = 0.0008). Our study suggests the prolactin receptor gene is a molecular target that may be important in the pathogenesis and progression of lobular neoplasia. Investigation of the status of this gene in cases of DCIS has indicated that it may not be as important in the progression of this type of breast cancer, supporting the view that lobular and ductal carcinomas may evolve along separate pathways.

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Acknowledgments

We would like to thank Dr Frances O’Malley (Mount Sinai Hospital, Toronto) for providing us cases for the microarray analysis. This study was supported by grants from the Dean’s Fund, Faculty of Medicine, University of Toronto and the Streams of Excellence Program of the Canadian Breast Cancer Research Alliance to S.J.D., the Canadian Institutes of Health Research (CIHR) Molecular Pathology Fellowship (STP-53912) and the Ontario Institute for Cancer Research (OICR) grant TSAO-OICR-RF-007 to D.T.T.

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Authors and Affiliations

  1. Campbell Family Institute for Breast Cancer Research, University Health Network, 200 Elizabeth Street, 11E444, Toronto, ON, M5G 2C4, Canada

    Danh Tran-Thanh & Susan J. Done

  2. Ontario Cancer Institute, University Health Network, Toronto, ON, Canada

    Nona C. Arneson & Keisha S. Warren

  3. Department of Pathology, University Health Network, Toronto, ON, Canada

    Danh Tran-Thanh, Ardit Deliallisi & Susan J. Done

  4. Division of Biostatistics, University Health Network, Toronto, ON, Canada

    Melania Pintilie

  5. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada

    Anita Bane

  6. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Susan J. Done

  7. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Susan J. Done

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  1. Danh Tran-Thanh
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  2. Nona C. Arneson
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  3. Melania Pintilie
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  4. Ardit Deliallisi
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  7. Susan J. Done
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Correspondence to Susan J. Done.

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Tran-Thanh, D., Arneson, N.C., Pintilie, M. et al. Amplification of the prolactin receptor gene in mammary lobular neoplasia. Breast Cancer Res Treat 128, 31–40 (2011). https://doi.org/10.1007/s10549-010-1025-6

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  • DOI: https://doi.org/10.1007/s10549-010-1025-6

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