Since immunohistochemistry (IHC) for protein markers is increasingly used to guide the choice of targeted therapies in cancer patients (for example, expression of the programmed death ligand-1 PD-L1 in selecting candidates for immunotherapy [18,19]); it is therefore timely and important for the cancer research community to acknowledge the influence of intra-tumor heterogeneity on biomarker outcome studies and to discuss reasonable frameworks to overcome potential bias. Here, CD274 is linked to cancer.