title: Visual assessment of Ki67 using a 5-grade scale (Eye-5) is easy and practical to classify breast cancer subtypes with high reproducibility.
abstract: OBJECTIVE
  Personalised breast cancer therapy requires pathological characterisation of tumours. The proliferative index, based on Ki67, is pivotal, but a standard method has not been established. Here we look for an easy and practical way to evaluate Ki67.
  
  
  METHODS
  Immunohistochemical staining of estrogen receptors, progesterone receptors, HER2 and Ki67 (MIB-1) was performed on resected specimens from 406 primary invasive ductal carcinomas. Ki67 labelling index (LI) from manual counting was compared with visual assessment using a 5-grade scale (Eye-5). Next, 10 pathologists evaluated 100 samples with marked hot spots by using Eye-5. Another 100 samples without marking were also assessed by eight pathologists. One year later, two pathologists reviewed 222 cases with Eye-5. Prognosis was analysed among estrogen receptor-positive cases with postoperative endocrine therapy.
  
  
  RESULTS
  Eye-5 showed good correlation to LI. All 136 cases of score 4-5 had LI >20% and all 56 cases of score 1 had LI<20%, which means that manual counting was not necessary for about half of the cases. Interobserver and intraobserver variability was low even when a hot spot was not fixed. Eye-5 also correlated with histological grade and lymph node metastasis. Combining Eye-5 and histological grade created a new algorism to predict LI, which allows 80% of all cases (74% of luminal cases) without manual counting. Cases of Eye-5 score 1-2 had significantly better survival than score 3-5.
  
  
  CONCLUSIONS
  Visual assessment of Ki67 by a 5-grade scale (Eye-5) is fast, easy, and reliable with acceptably low interobserver and intraobserver variability. Eye-5 can replace LI in many luminal tumours, and is a strong candidate as a standard method of evaluating Ki67.
authors: Department of Pathology, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan.
authors: Akira I
authors: AI
authors: Hida
authors: Department of Pathology, Saiseikai Imabari Hospital, Imabari, Ehime, Japan.
authors: Kenji
authors: K
authors: Bando
authors: Pathology Division, Ehime University Hospital, Toon, Ehime, Japan.
authors: Atsuro
authors: A
authors: Sugita
authors: Department of Pathology, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan.
authors: Toshiharu
authors: T
authors: Maeda
authors: Saiseikai Saijo Medical Center, Saijo, Ehime, Japan.
authors: Norifumi
authors: N
authors: Ueda
authors: Division of Pathology & Laboratory Medicine, Uwajima City Hospital, Uwajima, Ehime, Japan.
authors: Shoichi
authors: S
authors: Matsukage
authors: Division of Pathology & Laboratory Medicine, Uwajima City Hospital, Uwajima, Ehime, Japan.
authors: Mamoru
authors: M
authors: Nakanishi
authors: Department of Pathology, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan.
authors: Katsumi
authors: K
authors: Kito
authors: Pathology Division, Gifu University Hospital, Gifu, Japan.
authors: Tatsuhiko
authors: T
authors: Miyazaki
authors: Division of Pathology, Matsuyama-shimin Hospital, Matsuyama, Ehime, Japan.
authors: Yuji
authors: Y
authors: Ohtsuki
authors: Department of Pathology, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan.
authors: Yumi
authors: Y
authors: Oshiro
authors: Department of Breast Surgery, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan.
authors: Hiromichi
authors: H
authors: Inoue
authors: Department of Breast Surgery, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan.
authors: Hidetoshi
authors: H
authors: Kawaguchi
authors: Division of Clinical Biostatistics, Center for Clinical Research, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.
authors: Natsumi
authors: N
authors: Yamashita
authors: Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.
authors: Kenjiro
authors: K
authors: Aogi
authors: Department of Pathology 2, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors: Takuya
authors: T
authors: Moriya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001706:Biopsy; D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000145:classification / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D014796:Visual Perception
chemical_list: D019394:Ki-67 Antigen
keywords: BREAST CANCER; BREAST PATHOLOGY; TUMOUR BIOLOGY