These findings align with previous studies highlighting the prognostic power of spatial heterogeneity metrics, including Ki67 bimodality,12,19 Shannon entropy of Ki67%,10 and Haralick entropy for other biomarkers like PR12 and HER2.13 Spatial heterogeneity of mesenchymal-epithelial transition protein has also been shown to outperform average marker expression in predicting survival outcomes in colorectal cancer.24 Altogether, this evidence reinforces the broader adoption of spatial heterogeneity metrics for improving prognostic modeling. This evidence concerns the gene MKI67 and colorectal cancer.