title: Prognostic and predictive significance of proliferation in 867 colorectal cancers.
abstract: OBJECTIVE
  Recently, the Oncotype DX recurrence score, which measures a gene expression signature including markers of tumour proliferation, was validated as a prognostic signature in colorectal cancer. This study aimed to evaluate whether the Ki67 proliferation index can provide similar prognostic and predictive information.
  
  
  METHODS
  Tissue microarrays were constructed from triplicate cores of colorectal cancer. Immunohistochemistry for Ki67 was performed with the SP6 antibody and the percentage of positive tumour cells scored. Prognostic significance was evaluated in 867 cancers (601 events) using Cox proportional hazards models.
  
  
  RESULTS
  The Ki67 labelling index, divided at the median, was not a statistically or clinically significant prognostic factor in univariate analyses of 5-year overall survival (HR 0.98, 95% CI 0.84 to 1.15, p=0.84). Multivariate analyses were similarly non-significant. However, in Dukes' stage C patients, the high Ki67 subgroup derived a greater 5-year overall survival benefit from chemotherapy (HR 0.32, 95% CI 0.21 to 0.51, p<0.0001) than the low subgroup (HR 0.57, 95% CI 0.37 to 0.89, p=0.011).
  
  
  CONCLUSIONS
  The Ki67 proliferation index is not a useful prognostic factor in colorectal cancer, but deserves further evaluation as a predictive factor for the incremental benefit derived from adjuvant chemotherapy.
authors.affiliation: Department of Biostatistics, Genentech Inc., South San Francisco, California 94080, USA.
authors.forename: Imola K
authors.initials: IK
authors.lastname: Fodor
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Hutchins
authors.forename: Carmina
authors.initials: C
authors.lastname: Espiritu
authors.forename: Philip
authors.initials: P
authors.lastname: Quirke
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Jubb
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D046888:Tissue Array Analysis; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen