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Prognostic and predictive significance of proliferation in 867 colorectal cancers
  1. Imola K Fodor1,
  2. Gordon G Hutchins2,
  3. Carmina Espiritu3,
  4. Philip Quirke2,
  5. Adrian M Jubb3
  1. 1Department of Biostatistics, Genentech Inc., South San Francisco, California, USA
  2. 2Department of Tumour Biology and Pathology, Leeds Institute for Molecular Medicine, University of Leeds, Leeds, UK
  3. 3Department of Pathology, Genentech Inc., South San Francisco, California, USA
  1. Correspondence to Dr Adrian M Jubb, Department of Pathology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA; adrianj{at}


Aim 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.

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