title: Minichromosome maintenance protein 2 is a strong independent prognostic marker in breast cancer.
abstract: OBJECTIVE
  To test the hypothesis that prognostic information in breast cancer may be derived from an accurate assessment of epithelial cell cycle entry, as indicated by expression of minichromosome maintenance (MCM) proteins.
  
  
  METHODS
  We used immunohistochemistry to examine the distribution of Mcm-2 in breast tissue. Power calculations based on a pilot study of 67 whole tissue sections led to selection of an independent 347-core breast carcinoma tissue microarray validation set. We tested for associations between Mcm-2 (and Ki-67) labeling index (LI) and various clinicopathologic parameters.
  
  
  RESULTS
  Mcm-2 was expressed more frequently than the standard proliferation marker Ki-67 in whole tissue sections of normal breast (P =.0003) and breast carcinoma (P <.0001). In 221 assessable cores of invasive carcinoma, the Mcm-2 LI showed a positive association with tumor size (P =.002), mitotic index (P <.0001), histologic grade (P <.0001), and the Nottingham Prognostic Index (NPI) score (P <.0001). Using a cutoff value of 50%, Mcm-2 LI was associated with overall survival (P =.0007), disease-free interval (P =.0002), and with the development of regional recurrence (P =.011) and distant metastases (P =.0016). Cox regression analysis suggested that the Mcm-2 LI is a strong prognostic factor in breast cancer that is independent and superior to histologic grade, lymph node stage, and Ki-67 LI, but not the NPI score.
  
  
  CONCLUSIONS
  Mcm-2 may be of utility as a prognostic marker to refine the prediction of outcome in breast cancer, for example when combined with parameters currently used in the NPI.
authors.affiliation: Medical Research Council Cancer Cell Unit, Hutchison/Medical Research Council Research Centre, Hills Rd, Cambridge CB2 2XZ, United Kingdom. nc109@cam.ac.uk
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gonzalez
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.forename: Grace
authors.initials: G
authors.lastname: Callagy
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Vowler
authors.forename: Lesley S
authors.initials: LS
authors.lastname: Morris
authors.forename: Kate
authors.initials: K
authors.lastname: Bird
authors.forename: Jane A
authors.initials: JA
authors.lastname: Bell
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Laskey
authors.forename: Nicholas
authors.initials: N
authors.lastname: Coleman
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D004261:DNA Replication; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009361:Neoplasm Invasiveness / Q000175:diagnosis / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010865:Pilot Projects; D017697:Premenopause; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D064111:Minichromosome Maintenance Complex Component 2