Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists

Toru Morioka, Naoki Niikura, Nobue Kumaki, Shinobu Masuda, Takayuki Iwamoto, Kozue Yokoyama, Rin Ogiya, Risa Oshitanai, Mayako Terao, Banri Tsuda, Takuho Okamura, Yuki Saito, Yasuhiro Suzuki, Yutaka Tokuda

Research output: Contribution to journalArticle

Abstract

Background: Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown. Methods: We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test. Results: Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (κ 0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (p < 0.001) and obtained using image analysis (p = 0.031). Conclusions: The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBreast Cancer
DOIs
Publication statusAccepted/In press - Jun 29 2018

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Survival
Estrogen Receptors
Recurrence
Pathologists
Japan
Databases
Pathology
Breast Neoplasms
Sensitivity and Specificity
human ERBB2 protein
Clinical Decision-Making

Keywords

  • Antigen Ki-67
  • Breast cancer
  • Computer-assisted image analysis
  • Immunohistochemistry
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

Cite this

Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists. / Morioka, Toru; Niikura, Naoki; Kumaki, Nobue; Masuda, Shinobu; Iwamoto, Takayuki; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Okamura, Takuho; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka.

In: Breast Cancer, 29.06.2018, p. 1-10.

Research output: Contribution to journalArticle

Morioka, T, Niikura, N, Kumaki, N, Masuda, S, Iwamoto, T, Yokoyama, K, Ogiya, R, Oshitanai, R, Terao, M, Tsuda, B, Okamura, T, Saito, Y, Suzuki, Y & Tokuda, Y 2018, 'Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists', Breast Cancer, pp. 1-10. https://doi.org/10.1007/s12282-018-0885-1
Morioka, Toru ; Niikura, Naoki ; Kumaki, Nobue ; Masuda, Shinobu ; Iwamoto, Takayuki ; Yokoyama, Kozue ; Ogiya, Rin ; Oshitanai, Risa ; Terao, Mayako ; Tsuda, Banri ; Okamura, Takuho ; Saito, Yuki ; Suzuki, Yasuhiro ; Tokuda, Yutaka. / Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists. In: Breast Cancer. 2018 ; pp. 1-10.
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abstract = "Background: Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown. Methods: We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test. Results: Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (κ 0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (p < 0.001) and obtained using image analysis (p = 0.031). Conclusions: The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.",
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AU - Morioka, Toru

AU - Niikura, Naoki

AU - Kumaki, Nobue

AU - Masuda, Shinobu

AU - Iwamoto, Takayuki

AU - Yokoyama, Kozue

AU - Ogiya, Rin

AU - Oshitanai, Risa

AU - Terao, Mayako

AU - Tsuda, Banri

AU - Okamura, Takuho

AU - Saito, Yuki

AU - Suzuki, Yasuhiro

AU - Tokuda, Yutaka

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N2 - Background: Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown. Methods: We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test. Results: Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (κ 0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (p < 0.001) and obtained using image analysis (p = 0.031). Conclusions: The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.

AB - Background: Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown. Methods: We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test. Results: Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (κ 0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (p < 0.001) and obtained using image analysis (p = 0.031). Conclusions: The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.

KW - Antigen Ki-67

KW - Breast cancer

KW - Computer-assisted image analysis

KW - Immunohistochemistry

KW - Prognosis

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