[HEPATOLOGY] A Fibrous Stromal Component in Hepatocellular Carcinoma Reveals a Cholangiocarcinoma-Like Gene Expression Trait and Epithelial-Mesenchymal Transition

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap etween HCC and CC has been shown to comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common enomic trait of stem-cell–like proper-ties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests hat -HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like CC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression rofiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. -HCC expresses both CC-like and stem-cell–like genomic traits. In addition, we observed the expression of core epithelial-esenchymal transition (EMT)- related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of ransforming rowth factor beta (TGF-b) signaling was also found, implying its regula- tory role in the pathobiology of S-HCC. Conclusion: We uggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The xpression of stem-cell–like traits and TGF-b/EMT molecules may play a piv- otal role in the aggressive phenotyping of S-HCC. HEPATOLOGY 2012;55:1776-1786)