Interestingly, a previous study demonstrated more frequent expression of stemness markers in “scirrhous”

HCCs, compared to ordinary HCCs, and it was suggested that these stemness marker-expressing tumor cells may be involved in the fibrogenesis of these tumors.14, 22 It may, indeed, be possible that these tumor cells have the potential to produce fibrous stroma through the up-regulation of EMT-related markers. There is increasing evidence suggesting K19 as a progenitor cell marker. An extensive gene-expression profiling study demonstrated the presence of a “hepatoblast subtype” of human HCC, which was characterized by K19 expression, and was suggested to arise from hepatic progenitor cells,5 and, recently, a progenitor-derived HCC model was established in the CH5424802 rat, in which the K19-positive gene signature was well correlated with the former group of human HCCs.23 Furthermore, more than 15% of the genes in the K19 gene signature overlapped with the genes listed in the human embryonic stem cell-like module.23, 24 It is still uncertain whether the expression of K19 proteins in HCCs implies that these HCCs actually do carry stemness functions, as in the K19-positive ductular selleck chemicals llc reactions of the regenerating liver, or whether K19 expression in HCC is merely an epiphenomenon of poor differentiation. Indeed, some K19-positive HCCs were poorly differentiated tumors,

where it is possible that increasing genomic instability may have resulted in the expression of K19. Interestingly, a very recent study demonstrated that K19 gene activation may result in the expression of microRNA (miRNA)-492, and that this miRNA—and not the K19 protein

itself—may be responsible for the aggressive behavior of hepatoblastomas.25 K19 expression in HCCs may also have therapeutic implications; an association between the epidermal growth factor-epidermal growth factor receptor (EGFR) pathway and K19 expression in HCCs has recently been demonstrated, suggesting a possible role for therapeutic agents targeted against EGFR, such as Gefitinib and Erlotinib, in the treatment of this aggressive subset of HCCs.26 In conclusion, K19 positivity in HCC—which is easily detected by immunohistochemistry, and is medchemexpress reliable and reproducible—was well correlated with the clinicopathologic features of tumor aggressiveness and a poor prognosis, compared to other stemness-related proteins. K19 positivity in HCC was associated with increased expression of EMT and invasion-related proteins, both at the protein and mRNA level, and these results suggest that this subset of HCCs may acquire more invasive characteristics, compared to K19-negative HCCs, through the up-regulation of EMT and invasion-associated genes. Additional Supporting Information may be found in the online version of this article. “
“Transjugular intrahepatic portosystemic shunt (TIPS) is the mainstay treatment option for the complications of portal hypertension.