At the transcriptome level, consistent with our observation that increasing Ki-67 fraction is associated with the proportion of high-grade patterns observed at the whole tumour level (Fig. 1b), gene-set enrichment analyses revealed the greatest differential expression between high-grade and low/mid-grade predominant tumours involved genes related to cell cycle and cell proliferation (Fig. 1g, Methods), including upregulated G2M checkpoint, mTORC1 signalling and PI3K-AKT-mTOR signalling. Here, MKI67 is linked to neoplasm.