title: Histological grade as an alternative to the Ki67 labeling index is only available for luminal-type breast cancers.
abstract: BACKGROUND
  The 2011 St. Gallen Consensus Statement advocated using histological grade (HG) as a proliferation marker of breast cancer (BC) if reliable Ki67 labeling index (Ki67-LI) assessment is not available. However, it has been difficult to evaluate tumor aggressiveness in case of HG2.
  
  
  METHODS
  A total of 259 cases of BC were assessed for HG, Ki67-LI and other clinicopathological features. The cut point for Ki67-LI was interpreted as low and high using a 14% threshold.
  
  
  RESULTS
  The average age at diagnosis was 58.2 years (range 28-86); 64.9% of the patients were postmenopausal. Of the 259 cases, 151 were stage I, 78 were stage II, 29 were stage III, and 1 was stage IV. The subtypes based on immunohistochemical staining were 60 cases of luminal A (LA) type (23.2%), 37 cases of luminal B (LB) (HER2-) type (14.3%), 91 cases of LB (HER2+) type (35.1%), 40 cases of human epidermal growth factor receptor 2 (HER2) type (15.4%) and 31 cases of triple negative (TN) type (12%). HG was 1 (89 cases, 34.4 %), 2 (117 cases, 45.2%) and 3 (53 cases, 20.5%). High Ki67-LI cases were observed in HG1 (37.1%), HG2 (56.4%) and HG3 (96.2%). Especially in cases of HG2, high Ki67-LI cases were observed in 0 % of LA type, 100% of LB (HER2-) type, 71.2% of LB (HER2+) type, 68.8% of HER2 type and 40.0% of TN type. The average Ki67-LI was 6.0 ± 3.8 (LA type), 31.4 ± 15.7 [LB (HER2-) type], 20.2 ± 14.8 [LB (HER2+) type], 32.7 ± 21.9 (HER2 type) and 55.7 ± 32.2 (TN type). All LA-type cases and 66.7% of LB (HER2+)-type cases were low Ki67-LI.
  
  
  CONCLUSIONS
  Our study demonstrates that all LA-type cases and most HG1 of LB (HER2+)-type cases are low proliferative. However, HG was not informative enough for estimating tumor proliferation in cases of LB (HER2-), HER2 and TN types. It is necessary to add other proliferation tools such as the gene expression profiling tool and Ki67-LI except in LA and HG1 of LB (HER2+)-type cases.
authors.affiliation: Breast Center, Asahikawa Medical University Hospital, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan, shayashi@asahikawa-med.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sato
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Kei
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oikawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyokawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human