title: Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer: does the antibody matter?
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.
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest 1091, Hungary. Electronic address: acs.balazs.se@gmail.com.
authors.forename: Balázs
authors.initials: B
authors.lastname: Ács
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest 1091, Hungary. Electronic address: kulka.janina@med.semmelweis-univ.hu.
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest 1091, Hungary. Electronic address: kovacs.attila@med.semmelweis-univ.hu.
authors.forename: Kristóf Attila
authors.initials: KA
authors.lastname: Kovács
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest 1085, Hungary. Electronic address: telekiivett@gmail.com.
authors.forename: Ivett
authors.initials: I
authors.lastname: Teleki
authors.affiliation: MTA-SE Tumor Progression Research Group, 2nd Department of Pathology, Semmelweis University, Budapest 1091, Hungary. Electronic address: tokesa1972@yahoo.co.uk.
authors.forename: Anna-Mária
authors.initials: AM
authors.lastname: Tőkés
authors.affiliation: Institute of Physiology, University of Pécs, Pécs 7624, Hungary. Electronic address: agnes.meczker@aok.pte.hu.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Meczker
authors.affiliation: MTA-TTK Lendület Cancer Biomarker Research Group, Budapest 1117, Hungary; 2nd Department of Pediatrics, Semmelweis University, Budapest 1094, Hungary. Electronic address: zsalab2@yahoo.com.
authors.forename: Balázs
authors.initials: B
authors.lastname: Győrffy
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest 1091, Hungary. Electronic address: madaras.lilla@med.semmelweis-univ.hu.
authors.forename: Lilla
authors.initials: L
authors.lastname: Madaras
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, MTA-SE Tumor Progression Research Group, Budapest 1085, Hungary. Electronic address: krenacs.tibor@med.semmelweis-univ.hu.
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenács
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest 1091, Hungary; MTA-TTK Lendület Cancer Biomarker Research Group, Budapest 1117, Hungary. Electronic address: cac@korb2.sote.hu.
authors.forename: Attila Marcell
authors.initials: AM
authors.lastname: Szász
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D019394:Ki-67 Antigen / Q000032:analysis* / Q000276:immunology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000906:Antibodies; D019394:Ki-67 Antigen
keywords: Breast cancer; Concordance; Ki-67 antibody; Multivariate analysis; Prognosis