Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer: does the antibody matter?

Hum Pathol. 2017 Jul:65:31-40. doi: 10.1016/j.humpath.2017.01.011. Epub 2017 Feb 8.

Abstract

Although several antibodies are available for immunohistochemical detection of Ki-67, even the most commonly used MIB-1 has not been validated yet. Our aim was to compare 5 commercially available antibodies for detection of Ki-67 in terms of agreement and their ability in predicting prognosis of breast cancer. Tissue microarrays were constructed from 378 breast cancer patients' representative formalin-fixed, paraffin-embedded tumor blocks. Five antibodies were used to detect Ki-67 expression: MIB-1 using chromogenic detection and immunofluorescent-labeled MIB-1, SP-6, 30-9, poly, and B56. Semiquantitative assessment was performed by 2 pathologists independently on digitized slides. To compare the 5 antibodies, intraclass correlation and concordance correlation coefficient were used. All the antibodies but immunofluorescent-labeled MIB-1 (at 20% and 30% thresholds, P=.993 and P=.342, respectively) and B56 (at 30% threshold, P=.288) separated high- and low-risk patient groups. However, there were a significant difference (P values for all comparisons≤.005) and a moderate concordance (intraclass correlation, 0.645) between their Ki-67 labeling index scores. The highest concordance was found between MIB-1 and poly (concordance correlation coefficient=0.785) antibodies. None of the antibodies except Ki-67 labeling index as detected by poly (P=.031) at 20% threshold and lymph node status (P<.001) were significantly linked to disease-free survival in multivariate analysis. At 30% threshold, this was reduced to lymph node status (P<.001) alone. Our results showed that there are considerable differences between the different Ki-67 antibodies in their capacity to detect proliferating tumor cells and to separate low- and high-risk breast cancer patient groups.

Keywords: Breast cancer; Concordance; Ki-67 antibody; Multivariate analysis; Prognosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies / immunology*
  • Antibody Specificity
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cell Proliferation*
  • Disease-Free Survival
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry / methods*
  • Ki-67 Antigen / analysis*
  • Ki-67 Antigen / immunology
  • Lymphatic Metastasis
  • Middle Aged
  • Multivariate Analysis
  • Observer Variation
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors

Substances

  • Antibodies
  • Ki-67 Antigen