305 - Immunohistochemical Ki67 labeling index has a similar proliferation predictive power as various first-generation gene signatures in breast cancer

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Biomarkers
Breast Cancer
Presenter Naoki Niikura
Authors N. Niikura1, T. Iwamoto2, S. Masuda3, N. Kumaki4, M. Shirane5, K. Mori5, T. Okamura1, Y. Saito1, Y. Suzuki1, Y. Tokuda1
  • 1Breast And Endocrine Surgery, Tokai University School of Medicine, 259-1193 - Kanagawa/JP
  • 2Department Of Breast And Endocrine Surgery, Okayama University Hospital, Okayama/JP
  • 3Department Of Pathology, Nihon University School of Medicine, Tokyo/JP
  • 4Department Of Pathology, Tokai University School of Medicine, 259-1193 - Kanagawa/JP
  • 5Product Research, Chugai Pharmaceuticals Co. Ltd, Kanagawa/JP

Abstract

Background

Immunohistochemical assessment of Ki67 labeling index (IHC Ki67) has been described as a prognostic and predictive marker for breast cancer. On the other hand, several genetic prognostic markers have been described for breast cancer However, few clinical data sets provide information on correlations between genomic markers, mRNA Ki67, and IHC Ki67 in the same cohort of patients with survival data. The objective of this study is to examine the association between immunohistochemical Ki67 labeling index, Ki67 mRNA expression level, and first-generation gene signatures in a cohort of breast cancer patients.

Patients and methods

We assessed associations between IHC Ki67 and first-generation gene signatures in a panel of 40 tumor samples, using an oligonucleotide microarray. Gene expression analyses included Ki67 alone (MKi67), 21-gene signature, Mitosis Kinome score signature (MKS), and Genomic grade index (GGI). Correlation coefficients were calculated by Spearman's rank correlation test. To assess the relationship between IHC Ki67 and survival outcomes, survival curves were calculated by the Kaplan–Meier method and compared with the log-rank test according to IHC Ki67.

Results

Median age at diagnosis was 51 years. Treatments included adjuvant chemotherapy (32 patients) and endocrine therapy (21 patients). IHC Ki67, MKi67, and 3 genetic markers were highly correlated in all cases (Rho: 0.71–0.79). Estrogen receptor (ER)-positive cases exhibited strong correlations between IHC Ki67 and other signatures (Rho: 0.79–0.83). ER-negative cases displayed slightly lower correlations (Rho: 0.61–0.74). In ER-positive cases, the low IHC Ki67 group exhibited significantly longer relapse-free survival (RFS) than the high IHC Ki67 group (p = 0.007). This difference was confirmed by multivariate analysis.

Conclusions

Our data indicate that IHC Ki67 exhibits 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.

Disclosure

All authors have declared no conflicts of interest.