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

Breast Cancer Res Treat. 2011 Jun;127(3):591-9. doi: 10.1007/s10549-010-1028-3. Epub 2010 Jul 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / mortality
  • Cell Cycle Proteins
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Ki-67 Antigen / analysis*
  • Ki-67 Antigen / immunology
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Prognosis


  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Ki-67 Antigen