Breast Cancer Research and Treatment

, Volume 127, Issue 3, pp 639–648 | Cite as

Microcephalin is a new novel prognostic indicator in breast cancer associated with BRCA1 inactivation

  • Julie Richardson
  • Abeer M. Shaaban
  • Mohamed Kamal
  • Rawiah Alisary
  • Clare Walker
  • Ian O. Ellis
  • Valerie Speirs
  • Andrew R. Green
  • Sandra M. Bell
Preclinical study
First Online:
Received:
Accepted:

Abstract

The authors have investigated the expression of the microcephalin (MCPH1) protein to evaluate its prognostic importance in breast cancer. Microcephalin is a damage response protein involved in the regulation of BRCA1 and BRCA2. BRCA1 mutations are often associated with basal-like breast cancer, which are also often negative for oestrogen receptor (ER), progesterone receptor (PR) and HER2. MCPH1 immunohistochemistry was performed on 319 breast cancers prepared as tissue microarray and correlated with pathology, survival, ER, PR, HER2, EGFR, CK5/6, CK14 and BRCA1 expression. After performing continuous data analysis, mean microcephalin expression decreased with increasing grade (P < 0.006). Mean microcephalin expression was lower in ER/PR negative (P < 0.001) and triple negative cancers (P < 0.004). Conversely, an association with HER2-positive cancers was also identified (P < 0.034). Reduced microcephalin also correlated with reduced nuclear BRCA1 staining (P < 0.001). No association was identified with basal markers. After dichotomising the data into low and high microcephalin expression, reduced expression was identified in 29% (93/319) of breast cancers. An association with low expression was identified in invasive ductal carcinomas with breast cancer-specific survival (BCSS) (P = 0.052). Multivariate analysis of ductal carcinomas showed that microcephalin, together with lymph node involvement and tumour size were independent predictors of BCSS (P = 0.037). Microcephalin expression is reduced in 29% of breast cancers, particularly in higher grade tumours and BRCA1-negative cases. Microcephalin is an independent predictor of BCSS in invasive ductal breast cancer patients and may prove to be a useful biomarker for the identification of aggressive breast cancers.

Keywords

Microcephalin Breast cancer Immunohistochemistry HER2 Triple negative BRCA1 
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Notes

Acknowledgements

This study was supported by grants from Yorkshire Cancer Research grant number L317 (SMB & VS), and the Breast Cancer Campaign 2007NovPR53 (SMB & VS). MK is supported by a scholarship from the Egyptian government. RA is supported by a scholarship from the Saudi Arabian government.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Julie Richardson
    • 1
  • Abeer M. Shaaban
    • 2
  • Mohamed Kamal
    • 1
    • 4
  • Rawiah Alisary
    • 1
  • Clare Walker
    • 2
  • Ian O. Ellis
    • 3
  • Valerie Speirs
    • 1
  • Andrew R. Green
    • 3
  • Sandra M. Bell
    • 1
  1. 1.Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, St. James’s University HospitalLeedsUK
  2. 2.St James’s Institute of OncologySt James’s University HospitalLeedsUK
  3. 3.Department of Pathology, School of Molecular Medical SciencesUniversity of Nottingham and Nottingham University Hospitals NHS TrustNottinghamUK
  4. 4.Department of ZoologyUniversity of BenhaBenhaEgypt

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