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Breast Cancer Research and Treatment

, Volume 129, Issue 3, pp 703–716 | Cite as

Multicentric breast cancer: clonality and prognostic studies

  • R. Eeles
  • G. Knee
  • S. Jhavar
  • J. Mangion
  • S. Ebbs
  • G. Gui
  • S. Thomas
  • M. Coppen
  • R. A’Hern
  • S. Gray
  • C. Cooper
  • J. Bartek
  • J. Yarnold
Preclinical study

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.

Keywords

Multicentric Breast cancer Clonality TP53 Prognosis 

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

Notes

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).

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • R. Eeles
    • 1
    • 2
  • G. Knee
    • 3
  • S. Jhavar
    • 1
    • 2
  • J. Mangion
    • 1
    • 4
  • S. Ebbs
    • 2
  • G. Gui
    • 2
  • S. Thomas
    • 5
  • M. Coppen
    • 5
  • R. A’Hern
    • 1
  • S. Gray
    • 2
  • C. Cooper
    • 1
  • J. Bartek
    • 6
    • 7
  • J. Yarnold
    • 1
    • 2
  1. 1.The Institute of Cancer ResearchSurreyUK
  2. 2.Royal Marsden NHS Foundation TrustSurreyUK
  3. 3.Kingston HospitalKingston Upon ThamesUK
  4. 4.Bioinformatics Europe, SOLID Next Generation SequencingCheshireUK
  5. 5.Mayday University HospitalThornton HeathUK
  6. 6.Institute of Cancer Biology and Centre for Genotoxic Stress ResearchDanish Cancer SocietyCopenhagenDenmark
  7. 7.Laboratory of Genome Integrity and Institute of Molecular and Translational MedicinePalacky UniversityOlomoucCzech Republic

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