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 (Corresponding Author)

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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.

Original languageEnglish
Pages (from-to)639-648
Number of pages10
JournalBreast Cancer Research and Treatment
Volume127
Issue number3
Early online date15 Jul 2010
DOIs
Publication statusPublished - Jun 2011

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Keywords

  • BRCA1
  • Breast cancer
  • HER2
  • Immunohistochemistry
  • Microcephalin
  • Triple negative

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Richardson, J., Shaaban, A. M., Kamal, M., Alisary, R., Walker, C., Ellis, I. O., ... Bell, S. M. (2011). Microcephalin is a new novel prognostic indicator in breast cancer associated with BRCA1 inactivation. Breast Cancer Research and Treatment, 127(3), 639-648. https://doi.org/10.1007/s10549-010-1019-4