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Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-BRCA1/2 breast cancer patients

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Abstract

Glycodelin (encoded by PAEP gene) is a secreted lipocalin protein mainly expressed in reproductive tissues, but also in several tumour types. In the breast, glycodelin is expressed both in normal epithelial and cancerous tissue. To investigate the association of glycodelin with clinicopathological features of breast cancer and outcome of patients we evaluated the protein expression of glycodelin in a large series of breast tumours. Immunohistochemical analysis of tissue microarrays was used to study glycodelin expression on 399 sporadic and 436 familial non-BRCA1/2 tumours with strong family history. Gene expression analysis was used to define genes co-expressed with PAEP in sporadic and familial non-BRCA1/2 breast tumours. In the sporadic series, the glycodelin expression associated with low proliferation rate (P < 0.001), with a tendency towards well-differentiated tumours (grades 1 and 2, P = 0.012) and high cyclin D1 (P = 0.034) expression. However, in familial non-BRCA1/2 cases with strong family history glycodelin expression associated with a less favourable phenotype, i.e. positive lymph node status (P = 0.003) and HER2-positive tumours (P = 0.009). Moreover, the patients with glycodelin-positive tumours had an increased risk for distant metastases (P = 0.001) and in multivariate analysis glycodelin expression was an independent predictor of metastasis (hazard ratio (HR) = 2.22, 95% confidence interval (95% CI) = 1.22–4.03, P = 0.009) in familial non-BRCA1/2 breast cancer. Gene expression analysis further revealed different gene expression profiles correlating with the PAEP expression in the sporadic and familial non-BRCA1/2 breast cancers. Our findings suggest differential progression pathways in the sporadic and familial non-BRCA1/2 breast tumours expressing glycodelin.

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Acknowledgments

We thank Drs. Kirsimari Aaltonen and Karl von Smitten and RN Hanna Jäntti for their help with the patient data and specimens. The Finnish Cancer Registry is gratefully acknowledged for the cancer data. This work was supported by Helsinki University Central Hospital Research Fund, Academy of Finland (132473, 135937), the Finnish Cancer Society, the Sigrid Juselius Foundation and Magnus Ehrnrooth Foundation.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Biomedicum Helsinki, P.O. Box 700, FIN-00029, Helsinki, Finland

    Laura C. Hautala, Dario Greco, Tuomas Heikkinen & Heli Nevanlinna

  2. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland

    Päivi Heikkilä

  3. Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland

    Kristiina Aittomäki

  4. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland

    Carl Blomqvist

  5. Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

    Laura C. Hautala, Riitta Koistinen & Hannu Koistinen

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  1. Laura C. Hautala
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  2. Dario Greco
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  3. Riitta Koistinen
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Correspondence to Heli Nevanlinna.

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Hautala, L.C., Greco, D., Koistinen, R. et al. Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-BRCA1/2 breast cancer patients. Breast Cancer Res Treat 128, 85–95 (2011). https://doi.org/10.1007/s10549-010-1065-y

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  • DOI: https://doi.org/10.1007/s10549-010-1065-y

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