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

• Published in: Human pathology Vol. 65; pp. 31 - 40
• Main Authors: Ács, Balázs, Kulka, Janina, Kovács, Kristóf Attila, Teleki, Ivett, Tőkés, Anna-Mária, Meczker, Ágnes, Győrffy, Balázs, Madaras, Lilla, Krenács, Tibor, Szász, Attila Marcell
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2017; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies - immunology; Antibody Specificity; Automation; Biopsy; Breast cancer; Breast Neoplasms - chemistry; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer therapies; Cell cycle; Cell Proliferation; Chemotherapy; Concordance; Disease-Free Survival; Female; Fluorescent Antibody Technique; Gene expression; Histopathology; Humans; Immunoglobulins; Immunohistochemistry - methods; Ki-67 antibody; Ki-67 Antigen - analysis; Ki-67 Antigen - immunology; Lymphatic Metastasis; Medical prognosis; Middle Aged; Multivariate Analysis; Observer Variation; Pathology; Patients; Predictive Value of Tests; Prognosis; Proteins; Reproducibility; Reproducibility of Results; Retrospective Studies; Risk Assessment; Risk Factors; Software; Studies; Time Factors; Ki-67 antibody; Breast cancer; Prognosis; Multivariate analysis; Concordance
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2017.01.011

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. •SP6, 30-9, poly, B56, MIB-1, and immunofluorescent-labeled MIB-1 antibodies were compared.•Significant difference occurred between all Ki-67 LI assessments of the 5 antibodies.•Highest concordance/agreement was observed between MIB-1 and poly, and 30-9 and poly.•All investigated Ki-67 antibodies have prognostic potential except MIB-1–IF and B56.•Only poly antibody was an independent predictor of prognosis at 20% threshold.