title: Immunohistochemical Ki67 labeling index has similar proliferation predictive power to various gene signatures in breast cancer.
abstract: The objective of this study was to examine the association between the immunohistochemical Ki67 labeling index (IHC Ki67), Ki67 mRNA expression level, and first-generation gene signatures in a cohort of breast cancer patients. We assessed associations between IHC Ki67 and first-generation gene signatures in a panel of 39 tumor samples, using an oligonucleotide microarray. Gene expression analyses included Ki67 alone (MKi67), 21-gene signature, mitosis kinome score signature, and genomic grade index. Correlation coefficients were calculated by Spearman's rank correlation test. In all cases, IHC Ki67, MKi67, and three genetic markers were highly correlated (ρ, 0.71-0.97). Estrogen receptor (ER)-positive cases showed strong correlations between IHC Ki67 and other signatures (ρ, 0.79-0.83). The ER-negative cases showed slightly lower correlations (ρ, 0.58-0.73). In ER-positive cases, the low IHC Ki67 group showed significantly longer relapse-free survival than the high IHC Ki67 group (P = 0.007). This difference was confirmed by multivariate analysis. Our data indicate that IHC Ki67 shows similar predictive power for proliferation in ER-positive cancers as genomic markers. Further study of IHC Ki67 is needed to define prognostic factors and predictive factors for chemotherapy using central laboratory assessment.
authors.affiliation: Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Kanagawa, Japan. niikura@is.icc.u-tokai.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Niikura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Shinobu
authors.initials: S
authors.lastname: Masuda
authors.forename: Nobue
authors.initials: N
authors.lastname: Kumaki
authors.forename: Tang
authors.initials: T
authors.lastname: Xiaoyan
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Shirane
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mori
authors.forename: Banri
authors.initials: B
authors.lastname: Tsuda
authors.forename: Takuho
authors.initials: T
authors.lastname: Okamura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokuda
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone