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Multicentric breast cancer: clonality and prognostic studies

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Abstract

Clonality of multicentric breast cancer has traditionally been difficult to assess. We aimed to assess this using analysis of TP53 status (expression and mutation status). These results were then incorporated into an analysis of prognostic factors in multicentric tumours in a 10-year follow up study. Clonal status of multicentric breast cancer foci (n = 88 foci) was determined by immunohistochemical and molecular studies of TP53 in a total of 40 patients. Prognostic factors from these patients were also compared with 80 age- and stage-matched controls with unicentric breast cancer from the Royal Marsden NHS Foundation Trust Breast Cancer Database. Our results indicate that multicentric breast cancer foci were polyclonal within an individual patient in at least 10 patients (25%) with respect to immunohistochemical staining and in four patients (10%) with respect to abnormal band shifts on single strand conformational polymorphism (SSCP) molecular analysis. No individual variable was predictive of multicentric or unicentric disease. However, there was a worse overall survival in the multicentric breast cancer patients in whom at least two cancer foci stained positively on TP53 immunohistochemistry compared with the matched control group (P = 0.04). In conclusion, these results suggest that a proportion of multicentric breast cancer foci are polyclonal with respect to TP53 status and that TP53 over-expression predicts for a poorer prognosis in multicentric breast cancer.

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Abbreviations

SSCP:

Single strand conformational polymorphism

DCIS:

Ductal carcinoma in situ

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

IPTG:

Isopropyl-β-d-thiogalactopyranoside

CDGE:

Constant denaturant gel electrophoresis

CASH:

Cancer and steroid hormone study

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Acknowledgments

The authors are grateful to the late Prof J Sloane and Mr U Querci della Rovere and Dr M Kershaw for pathology expertise and referrals respectively, Dr I McGrath for referrals. We are grateful to Mrs Sue Clinton and Ms Liz Philp for cutting the sections. The authors would like to thank Dr A Nash for referrals and Professor Sir David Lane for kind donation of the TP53 antibodies. This work was supported by The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, The Mayday University Hospital and The European Commission (Projects ‘Active p53’, ‘Infla-Care’ and ‘Biomedreg-CZ.1.05/2.1.00/01.0030’ to Prof Bartek). The authors would like to thank Elizabeth Page for her assistance with formatting the paper for submission. We acknowledge support of The NIHR to The Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust.

Conflict of interest

Prof Eeles has received educational grants from Astra Zeneca and Tepnel (now GenProbe).

Author information

Authors and Affiliations

  1. The Institute of Cancer Research, Cotswold Road, Sutton, Surrey, SM2 5NG, UK

    R. Eeles, S. Jhavar, J. Mangion, R. A’Hern, C. Cooper & J. Yarnold

  2. Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK

    R. Eeles, S. Jhavar, S. Ebbs, G. Gui, S. Gray & J. Yarnold

  3. Kingston Hospital, Galsworthy Road, Kingston Upon Thames, KT2 7QB, UK

    G. Knee

  4. Bioinformatics Europe, SOLID Next Generation Sequencing, Lingley House, 120 Birchwood Boulevard, Warrington, Cheshire, WA3 7QH, UK

    J. Mangion

  5. Mayday University Hospital, Mayday Road, Thornton Heath, CR7 7YE, UK

    S. Thomas & M. Coppen

  6. Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, Copenhagen, Denmark

    J. Bartek

  7. Laboratory of Genome Integrity and Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czech Republic

    J. Bartek

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  1. R. Eeles
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  2. G. Knee
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Corresponding author

Correspondence to R. Eeles.

Additional information

Bartek J, Yarnold J—joint senior authors.

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Eeles, R., Knee, G., Jhavar, S. et al. Multicentric breast cancer: clonality and prognostic studies. Breast Cancer Res Treat 129, 703–716 (2011). https://doi.org/10.1007/s10549-010-1230-3

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  • DOI: https://doi.org/10.1007/s10549-010-1230-3

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