title: Comparison of visual assessment and image analysis in the evaluation of Ki-67 expression and their prognostic significance in immunohistochemically defined luminal breast carcinoma.
abstract: OBJECTIVE
  To compare the Ki-67 labeling index value obtained through immunohistochemistry analysis by human examiners to that obtained from computer-assisted image analysis, and to establish a cut-off value for Ki-67 labeling index for each method in luminal B breast carcinoma.
  
  
  METHODS
  Immunohistochemistry analysis for Ki-67 was performed on the formalin-fixed, paraffin-embedded tissue samples from 403 patients with primary luminal breast cancers. Whole slide images were obtained using the NanoZoomer (Hamamatsu Photonics, Hamamatsu, Japan) and thoroughly analyzed using the Definiens Tissue Studio version 1.1 (Definiens AG, Munich, Germany) to detect the percentage of positively-stained nuclei of carcinoma cells.
  
  
  RESULTS
  Although a significant correlation was found between the Ki-67 labeling index obtained by manual assessment and computer-assisted image analysis (Spearman rank correlation coefficient, P < 0.01), the Ki-67 labeling index value obtained by manual assessment was significantly higher than that obtained by computer-assisted image analysis (Wilcoxon signed rank test, P < 0.0001). Disease-free survival was significantly lower in 403 patients with tumors having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.00001) and visual counting (cut-off value: 28.5%; P < 0.00001). Disease-free survival was also significantly lower in 288 patients who received adjuvant endocrine therapy alone having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.0001) and visual counting (cut-off value: 19.7%, P < 0. 0001).
  
  
  CONCLUSIONS
  The Ki-67 labeling index values determined by automated analysis and visual counting could equally predict disease-free survival in patients with luminal B breast carcinoma, including those who received endocrine therapy.
authors: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima arihiro@hiroshima-u.ac.jp.
authors: Koji
authors: K
authors: Arihiro
authors: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima.
authors: Miyo
authors: M
authors: Oda
authors: Department of Breast Surgery, Hiroshima Prefectural Hospital, Hiroshima.
authors: Masahiro
authors: M
authors: Ohara
authors: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima.
authors: Takayuki
authors: T
authors: Kadoya
authors: Department of Breast Oncology, International Medical Center, Saitama Medical University, Hidaka.
authors: Akihiko
authors: A
authors: Osaki
authors: Department of Anatomical Pathology, Hiroshima Prefectural Hospital, Hiroshima, Japan.
authors: Takashi
authors: T
authors: Nishisaka
authors: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima.
authors: Noriyuki
authors: N
authors: Shiroma
authors: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima.|Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima.
authors: Yoshie
authors: Y
authors: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Ki-67; breast cancer; image analysis; immunohistochemistry; whole slide image