In all H&E stains, red ‘T’ indicates tumor tissue, while blue ‘N’ indicates normal tissue. Orientation of tumor/normal tissue is mirrored in bottom panel. (A) H&E-stained section shows clear cell renal cell carcinoma (top left, KIRC Sample 1 from Figure 7—source data 1) with the classical features of tumor nests with clear cytoplasm, separated by intricate, branching vascular septae, and adjacent non-neoplastic renal parenchyma (lower right). (B) KIRC Sample 1 immunohistochemical staining with MITO Ab2 antibody reveals markedly lower mitochondrial content (cytoplasmic, brown granular positivity) in clear cell RCC compared to normal tubules. (C) H&E-stained section shows papillary renal cell carcinoma type 1 (KIRP Sample 3) with tumor (top right) and normal tubules (lower left). (D) KIRP Sample 3 immunohistochemical stain with MITO Ab2 antibody shows KIRP with a slightly weaker positivity compared to normal tubules. (E) H&E-stained section showing invasive high grade urothelial carcinoma (lower left) with sheets of tumor cells in the lamina propria and the overlying normal urothelium (top right). (F) Immunohistochemical staining with MITO Ab2 antibody reveals slightly higher mitochondrial staining in urothelial carcinoma compared to normal urothelium.