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BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High-Grade Serous Carcinoma
  1. Tara Byrne, MPharm, PhD*,
  2. Laura Nelson, PhD*,
  3. James P. Beirne, MB, MRCOG, PhD,
  4. Daniel Sharpe, PhD*,
  5. Jennifer E. Quinn, PhD,
  6. W. Glenn McCluggage, FRCPath,
  7. Tracy Robson, PhD§ and
  8. Fiona Furlong, PhD*
  1. * School of Pharmacy and
  2. Centre for Cancer Research and Cell Biology, Queen's University Belfast; and
  3. Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom; and
  4. § Molecular and Cellular Therapeutics, Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland.
  1. Address correspondence and reprint requests to Fiona Furlong, PhD, School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT97BL, Northern Ireland, United Kingdom. E-mail: f.furlong{at}qub.ac.uk.

Abstract

Objectives The aim of this study was to investigate the relationship between BRCA1 and mitotic arrest deficiency protein 2 (MAD2) protein expression, as determined by immunohistochemistry, and clinical outcomes in epithelial ovarian carcinoma (EOC).

Methods A tissue microarray consisting of 94 formalin-fixed paraffin-embedded EOC with fully matched clinicopathological data were immunohistochemically stained with anti-BRCA1 and anti-MAD2 antibodies. The cores were scored in a semiquantitative manner evaluating nuclear staining intensity and extent. Coexpression of BRCA1 and MAD2 was evaluated, and patient survival analyses were undertaken.

Results Coexpression of BRCA1 and MAD2 was assessed in 94 EOC samples, and survival analysis was performed on 65 high-grade serous carcinomas (HGSCs). There was a significant positive correlation between BRCA1 and MAD2 expression in this patient cohort (P < 0.0001). Both low BRCA1 and low MAD2 are independently associated with overall survival because of HGSC. Low coexpression of BRCA1 and MAD2 was also significantly associated with overall survival and was driven by BRCA1 expression.

Conclusion BRCA1 and MAD2 expressions are strongly correlated in EOC, but BRCA1 expression remains the stronger prognostic factor in HGSC.

  • BRCA1
  • Immunohistochemistry
  • MAD2
  • Prognosis
  • Serous ovarian carcinomas

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Footnotes

  • The authors declare no conflicts of interest.

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