Breast Cancer Research and Treatment

, Volume 127, Issue 3, pp 591–599

MIB1/Ki-67 labelling index can classify grade 2 breast cancer into two clinically distinct subgroups

Authors

  • Mohammed A. Aleskandarany
    • Division of Pathology, School of Molecular Medical Sciences, Queen’s Medical CentreUniversity of Nottingham
    • Pathology Department, Faculty of MedicineMenoufyia University
  • Emad A. Rakha
    • Department of PathologyNottingham University Hospitals NHS Trust
  • R. Douglas Macmillan
    • Breast InstituteNottingham University Hospitals NHS Trust
  • Desmond G. Powe
    • Department of PathologyNottingham University Hospitals NHS Trust
  • Ian O. Ellis
    • Division of Pathology, School of Molecular Medical Sciences, Queen’s Medical CentreUniversity of Nottingham
    • Department of PathologyNottingham University Hospitals NHS Trust
    • Division of Pathology, School of Molecular Medical Sciences, Queen’s Medical CentreUniversity of Nottingham
Preclinical study

DOI: 10.1007/s10549-010-1028-3

Cite this article as:
Aleskandarany, M.A., Rakha, E.A., Macmillan, R.D. et al. Breast Cancer Res Treat (2011) 127: 591. doi:10.1007/s10549-010-1028-3

Abstract

Histological grade is recognized as one of the strongest prognostic factors in operable breast cancer (BC). Although grade 1 and grade 3 tumours are biologically and clinically distinct, grade 2 tumours bear considerable difficulty in outcome prediction and planning therapies. Several attempts such as genomic grade index have been performed to subclassify grade 2 into two subgroups with clinical relevance. Here, we present evidence that the routinely evaluable immunohistochemical MIB1/Ki67 labelling index (MIB-LI) can classify grade 2 tumours into two clinically distinct subgroups. In this study, growth fractions of 1,550 primary operable invasive breast carcinomas were immunohistochemically assayed on full-face tissue sections using the MIB1 clone of Ki-67. Growth fractions were assessed as number of MIB1 positive nuclei in 1,000 tumour nuclei at high-power magnification and expressed as MIB1-LI. Using a 10% cut-point of MIB1-LI, grade 2 BCs were classified into low (49.8%) and high (50.2%) proliferative subgroups. Univariate and multivariate survival analysis revealed statistically significant differences between these subgroups regarding patients’ BC specific survival (P < 0.001), and metastasis free survival (P < 0.001) which was independent of the well-established prognostic factors (HR = 2.944, 95% CI = 1.634–5.303, P < 0.001). In conclusion, our results further demonstrate that grade 2 BCs may represent at least two biological or behaviourally different entities. Assay of growth fraction in BC using MIB1/Ki67 immunohistochemistry is a robust cost-effective diagnostic tool that subdivides grade 2 tumours into low and high risk populations providing additional prognostic information in planning therapies and outcome prediction.

Keywords

Breast carcinomaGrowth fractionGradeImmunohistochemistryKi67

Copyright information

© Springer Science+Business Media, LLC. 2010