Upregulation of FGF21 expression in human hepatic tissues during HCC development. The expression levels of FGF21 were assessed by IHC (cytosolic maroon or orange stains) with anti-FGF21 antibody in the liver tissue sections from human patients as described in the Methods section. Representative images taken by light microscopy were shown for the following disease conditions: (A) grade 1 HCC tissues and (B) the tumor-adjacent (≥1.5 cm from the edge of tumor foci) hepatic tissues, (C) grade 2 HCC tissues and (D) the tumor-adjacent hepatic tissues, (E) grade 3 HCC tissues and (F) the tumor-adjacent hepatic tissues. This is in contrast to the normal hepatic tissues from healthy individuals (G), and phenotypically normal liver tissues (H) from the HCC patients. Low-magnification (×100) images are on the left, and black-boxed sections are enlarged (×1000) on the right. Green arrowhead: concentrated cytoplasmic FGF21 staining; Yellow arrow: enlarged or irregular nucleus; Blue arrow: fibrotic cirrhotic area.