title: Interobserver concordance of Ki67 labeling index in breast cancer: Japan Breast Cancer Research Group Ki67 ring study.
abstract: The standardized assessment of Ki67 labeling index (LI) is of clinical importance to identify patients with primary breast cancer who could benefit from chemotherapy. In this study, we evaluated the interobserver concordance of Ki67 LI assessment. Six surgical pathologists participated and all the slides were prepared from archival breast cancer tissues fixed in 10% buffered formalin for 24 h and stained with MIB-1. Three independent studies were conducted. In the first study, 30 stained slides were assessed using two different methods: the scoring system, with a positive rate scored from 1 (0-9%) to 10 (90-100%) by visual estimate; and the counting method, with approximately 1000 cells counted in hot spots. In the second study, 20 tumors with Ki67 LI 5-25% were assessed, and in the third study, 15 printed photographs of stained slides were assessed to avoid variations by selecting different fields. In study 1, the counting system (intraclass correlation coefficient [ICC], 0.66 [95% confidence interval 0.52-0.78]) demonstrated a better correlation than the scoring system (ICC, 0.57 [0.42-0.72]). In study 2, the assessment for Ki67 LI of 5-25% demonstrated a correlation (ICC, 0.68 [0.50-0.81]) similar to that of study 1 (unrestricted range of Ki67 LI). In study 3, the assessment of Ki67 LI by counting yielded a good concordance (ICC, 0.94 [0.88-0.97]). In conclusion, there was better concordance with the counting system, and concordance was high when the assessed field was predetermined, indicating that the selection of the evaluation area is critical for obtaining reproducible Ki67 LI in breast cancer.
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mikami
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ueno
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurosumi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Masuda
authors.forename: Rie
authors.initials: R
authors.lastname: Horii
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D007564:Japan; D019394:Ki-67 Antigen / Q000378:metabolism*; D015588:Observer Variation; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D019394:Ki-67 Antigen
references.citation: Cancer Sci. 2013 Nov;104(11):1539-43
references.pmid: 23905924
references.citation: Oncologist. 2008 Dec;13(12):1235-45
references.pmid: 19091781
references.citation: Lancet. 1995 Oct 21;346(8982):1085-7
references.pmid: 7564793
references.citation: J Natl Cancer Inst. 2008 Feb 6;100(3):207-12
references.pmid: 18230798
references.citation: Eur J Cancer. 2010 Aug;46(12):2216-24
references.pmid: 20471822
references.citation: Ann Oncol. 2011 Mar;22(3):582-587
references.pmid: 20716629
references.citation: J Natl Cancer Inst. 2011 Nov 16;103(22):1656-64
references.pmid: 21960707
references.citation: Clin Cancer Res. 2004 Oct 1;10(19):6622-8
references.pmid: 15475452
references.citation: J Natl Cancer Inst. 2009 May 20;101(10):736-50
references.pmid: 19436038
references.citation: Breast Cancer Res Treat. 2010 Jan;119(2):315-23
references.pmid: 19247830
references.citation: Ann Oncol. 2011 Aug;22(8):1736-47
references.pmid: 21709140
references.citation: Cancer. 1993 Jun 15;71(12):3926-31
references.pmid: 8508358
references.citation: J Clin Oncol. 2009 Jun 10;27(17):2809-15
references.pmid: 19380452
references.citation: Biometrics. 1977 Mar;33(1):159-74
references.pmid: 843571
references.citation: BMC Cancer. 2010 Oct 07;10:534
references.pmid: 20925963
references.citation: J Clin Oncol. 2007 Nov 20;25(33):5287-312
references.pmid: 17954709
references.citation: Lancet. 2012 Feb 4;379(9814):432-44
references.pmid: 22152853
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1168-76
references.pmid: 19204205
references.citation: Eur J Cancer. 2006 Nov;42(17):2954-60
references.pmid: 16935488
references.citation: Lancet Oncol. 2010 Feb;11(2):174-83
references.pmid: 20152769
references.citation: Breast Cancer Res Treat. 2009 Jul;116(1):53-68
references.pmid: 18592370
references.citation: Ann Oncol. 1999 Aug;10(8):993-6
references.pmid: 10509165
references.citation: Am J Clin Pathol. 2008 Dec;130(6):883-91
references.pmid: 19019764
references.citation: J Clin Oncol. 2008 Dec 1;26(34):5569-75
references.pmid: 18981464
references.citation: Breast Cancer Res. 2008;10(2):R30
references.pmid: 18380893
references.citation: Clin Cancer Res. 2005 Jan 15;11(2 Pt 2):951s-8s
references.pmid: 15701892
references.citation: Ann Oncol. 2012 Sep;23 Suppl 10:x219-27
references.pmid: 22987966
references.citation: Br J Cancer. 2001 Oct 19;85(8):1106-12
references.pmid: 11710821