Fig. 1.Two contrasting hepatocytic phospho-Smad signaling patterns were present
among liver specimens from patients wtih PBC: pSmad3L-dominant and pSmad3C
dominant. (A) Patient 5 in Supplementary Table 1, free of HCC development during
7.5 years following histopathologic diagnosis of PBC. Hepatocytes showed
considerable level of pSmad3C ( pSmad3C column), but scant level of
pSmad3L ( pSmad3L column). (B) Patient 44 in Supplementary Table 1, had
onset of HCC within 5 years after liver biopsy. Smad3 in hepatocytic nuclei was
sparsely phosphorylated in the C-terminal region ( pSmad3C column) but
highly phosphorylated in the linker region ( pSmad3L column). (C)
Cirrhotic liver specimen from patient 49 in Supplementary Table 1, who was
diagnosed with HCC when liver biopsy was performed. Phosphorylation of Smad3L was
high, while C-terminal phosphorylation of Smad3 was low. (D) Cirrhotic liver
specimen from patient 41 in Supplementary Table 1, No HCC arose during 12.8 years
after liver biopsy. Hepatocytic nuclei showed low phosphorylation at Smad3C and
low phosphorylation at Smad3L. Scale bars: 50 M. Formalin-fixed,
paraffin-embedded sections of liver specimens were stained with anti-pSmad3L
antibody ( pSmad3L column) and anti-pSmad3C antibody (
pSmad3C column), as described in the Methods section.