title: Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors--a surrogate marker?
abstract: BACKGROUND
  The number of mitoses and, thus, the proliferative capacity of a tumor is one of the most crucial variables for tumor grading. The Ki-67 nuclear antigen may be considered as an alternative to mitotic counts in grading schemes and as a single parameter that can be used in fine-needle aspirates and small biopsies.
  
  
  METHODS
  Immunohistochemistry using the anti-Ki-67 antibody MIB-1 was performed on 434 breast carcinoma specimens from the International Breast Cancer Study Group (formerly Ludwig) Trial V. Three groups based on Ki-67 percent were used to replace the mitotic counts component in the Nottingham grade (NHG) to produce the Nottingham/Ki-67 grade (NKG) and to assess Ki-67 as a single parameter.
  
  
  RESULTS
  In both the lymph node positive subgroup and the lymph node negative subgroup, the NKG and Ki-67 group was correlated significantly with Bloom-Richardson grade (BRG), NHG, and Nottingham type. Tumor size in the lymph node negative cohort and estrogen receptor status, progesterone receptor status, and c-erbB-2 expression in the lymph node positive cohort also were correlated significantly with NKG. Ki-67 percentage was correlated significantly with c-erbB-2 expression in the lymph node positive cohort only. NKG was similar to BRG and NHG when it was evaluated for prognostic significance. Patients with higher categoric Ki-67 percentages had worse overall and disease free survival in all groups except for the untreated, lymph node negative group.
  
  
  CONCLUSIONS
  Ki-67 detection represents a valuable tool and is a good objective substitute for mitotic counts when used in a grading system. When it is used alone, Ki-67 detection provides valuable information, although it is necessary to combine this with other parameters in the study of core biopsies and fine-needle aspirates.
authors.affiliation: International Breast Cancer Study Group Pathology Center, Western Infirmary, Glasgow, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Trihia
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.forename: Karen
authors.initials: K
authors.lastname: Price
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Rastko
authors.initials: R
authors.lastname: Golouh
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: John
authors.initials: J
authors.lastname: Collins
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Barry A
authors.initials: BA
authors.lastname: Gusterson
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D015999:Multivariate Analysis; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D019394:Ki-67 Antigen