International validation of the consensus Immunoscore for the classification of colon cancer

An international consortium of 14 centres in 13 countries assessed the consensus Immunoscore assay in patients with TNM stage I-III colon cancer, randomly assigned to training, internal validation and external validation sets. Paraffin sections of the tumour and invasive margin were processed by immunohistochemistry and the densities of CD3-positive and cytotoxic CD8-positive T cells quantified by digital pathology, with an Immunoscore derived from the mean of four density percentiles. Tissue from 3,539 patients was processed and 2,681 included after quality control. The assay was highly reproducible between observers and centres. In the training set, patients with a high Immunoscore had the lowest risk of recurrence at 5 years (8% against 19% intermediate and 32% low; hazard ratio 0.20 for high against low), and the findings were confirmed in both validation sets. In stratified multivariable analysis the association with time to recurrence was independent of age, sex, T stage, N stage, microsatellite instability and existing prognostic factors.