Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between 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 genomic trait of stem cell-like properties 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 that S-HCC may harbor common intermediate traits between HCC and CC including stem cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem cell-like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Over-expression of transforming growth factor β (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene expression traits in HCC. The expression of stem cell-like traits and TGF-β/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC.

A fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and EMT

M. Roncalli;
2012

Abstract

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between 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 genomic trait of stem cell-like properties 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 that S-HCC may harbor common intermediate traits between HCC and CC including stem cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem cell-like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Over-expression of transforming growth factor β (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. Conclusion: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene expression traits in HCC. The expression of stem cell-like traits and TGF-β/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11699/996
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