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Assessment of the Ki67 labeling index: a Japanese validation ring study

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Abstract

Background

A lack of consistent methods to evaluate Ki67 expression is problematic in terms of accurately predicting prognosis in breast cancer. Accordingly, this study aimed to identify the causes of discrepancies in Ki67 labeling index measurements by different observers under different conditions using breast cancer samples.

Patients and methods

This Japanese study group compared and assessed immunohistochemical (IHC) analysis of the Ki67 labeling index when measured by different pathologists. Six pathologists (pathologists A–F) in Japan participated in this ring study. One hundred and ten surgical cases of estrogen receptor-positive and human epidermal growth factor receptor 2-negative invasive breast cancer treated in 2007 were identified from the breast cancer database of Tokai University Hospital and were included in this study.

Results

For all 6 pathologists, the Ki67 labeling index were significantly different between grade 3 and grade 1 cases and between grade 3 and grade 2 cases, whereas the index tended to be different between grade 1 and grade 2 cases. Further, the Ki67 labeling indexes measured by the 6 pathologists were strongly correlated (ρ: 0.73–0.88). The IHC scores recorded by pathologist A were in moderate to good agreement with those recorded by the others in patients with a Ki67 labeling index of <13.25 % and in those with a Ki67 labeling index of >13.25 % (κ = 0.429–0.660). The Ki67 low and high concordance rates between pathologist A and the others were 0.452–0.778 and 0.862–0.979, respectively. The most pertinent reason for discrepancy in scores seemed to be the selection of the area for counting and the quality of nuclear staining.

Conclusion

The Ki67 labeling index measured by 6 pathologists without method standardization was in fair to good agreement. We plan to undertake a second ring study, pending recommendations by the international Ki67 panel.

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Acknowledgments

This work was supported by a research fund from the Japanese Breast Cancer Society.

Conflict of interest

There are no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Naoki Niikura

  2. Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan

    Nobue Kumaki

  3. Study Group of Standard Measurement of Ki67, The Japanese Society of Breast Cancer, Tokyo, Japan

    Naoki Niikura, Takashi Sakatani, Nobuyuki Arima, Yasuyo Ohi, Naoko Honma, Naoki Kanomata, Kazuya Yoshida, Takayuki Kadoya, Kentaro Tamaki & Takuya Moriya

  4. Department of Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Takashi Sakatani

  5. Department of Pathology, Kumamoto City Hospital, Kumamoto, Japan

    Nobuyuki Arima

  6. Department of Pathology, Hakuaikai Medical Corporation, Sagara Hospital, Kagoshima, Japan

    Yasuyo Ohi

  7. Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Naoko Honma

  8. Department of Pathology, Kawasaki Medical School, Kurashiki, Okayama, Japan

    Naoki Kanomata & Takuya Moriya

  9. Breast Center, Northern Fukushima Medical Center, Fukushima, Japan

    Kazuya Yoshida

  10. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima, Japan

    Takayuki Kadoya

  11. Department of Breast Surgery, Nahanishi Clinic, Okinawa, Japan

    Kentaro Tamaki

  12. Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan

    Takayuki Iwamoto

  13. Department of Breast Surgery, Kansai Medical University Hirakata Hospital, Hirakata, Japan

    Tomoharu Sugie

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  1. Naoki Niikura
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  2. Takashi Sakatani
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Correspondence to Naoki Niikura.

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Niikura, N., Sakatani, T., Arima, N. et al. Assessment of the Ki67 labeling index: a Japanese validation ring study. Breast Cancer 23, 92–100 (2016). https://doi.org/10.1007/s12282-014-0536-0

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  • DOI: https://doi.org/10.1007/s12282-014-0536-0

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