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

Balázs Ács, J. Kulka, Kristóf Attila Kovács, Ivett Teleki, A. Tőkés, Ágnes Meczker, B. Györffy, Lilla Madaras, T. Krenács, A. Szász

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalHuman Pathology
Volume65
DOIs
Publication statusPublished - Jul 1 2017

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Breast Neoplasms
Antibodies
Lymph Nodes
Patient Advocacy
Paraffin
Formaldehyde
Disease-Free Survival
Neoplasms
Multivariate Analysis

Keywords

  • Breast cancer
  • Concordance
  • Ki-67 antibody
  • Multivariate analysis
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer : does the antibody matter? / Ács, Balázs; Kulka, J.; Kovács, Kristóf Attila; Teleki, Ivett; Tőkés, A.; Meczker, Ágnes; Györffy, B.; Madaras, Lilla; Krenács, T.; Szász, A.

In: Human Pathology, Vol. 65, 01.07.2017, p. 31-40.

Research output: Contribution to journalArticle

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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.",
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