Proliferation marker MIB-1 correlates well with proliferative activity evaluated by BrdU in breast cancer: an immunohistochemical study including correlation with PCNA, p53, c-erbB-2 and estrogen receptor status

Pathol Int. 1996 Dec;46(12):953-61. doi: 10.1111/j.1440-1827.1996.tb03574.x.


The proliferative activity of 30 cases of non-treated invasive ductal breast carcinoma was evaluated by bromodeoxyuridine (BrdU), proliferation marker (MIB-1) and proliferating cell nuclear antigen (PCNA), and the relation between these proliferation markers and histological subtype and histological grade were investigated. In addition, the association of these proliferation markers with overexpression of p53 protein, c-erbB-2 oncoprotein, estrogen receptor (ER) status and clinicopathologic findings were also examined. The BrdU labeling index (LI), MIB-1 score and PCNA labeling rate (LR) correlated with the histological grade. However, there was no statistical difference in proliferative activity among the histological subtypes. A linear strong correlation was demonstrated between BrdU LI and MIB-1 score (r = 0.732). Significant correlation was also found between BrdU LI and PCNA LR (r = 0.446); however, the relation between MIB-1 score and PCNA LR was weak. BrdU LI and MIB-1 score correlated positively with tumor size, TNM stage and overexpression of p53, and negatively with the presence of ER. PCNA LR correlated only with p53. These results indicate that MIB-1 is closely associated with BrdU in clinicopathologic findings and is a more useful tool for evaluating cell proliferation than PCNA. However, it will be necessary to consider the clinical significance of MIB-1 immunohistochemistry cautiously until further widespread clinical and pathological studies are performed.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antigens, Nuclear
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Bromodeoxyuridine / metabolism*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology*
  • Cell Division
  • DNA / biosynthesis
  • DNA Replication
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism*
  • Tumor Suppressor Protein p53 / metabolism


  • Antigens, Nuclear
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • Receptors, Estrogen
  • Tumor Suppressor Protein p53
  • DNA
  • Receptor, ErbB-2
  • Bromodeoxyuridine