Hypervascular hepatocellular carcinomas showing hyperintensity on hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging: a possible subtype with mature hepatocyte nature.

PURPOSE

We evaluated molecular features of hypervascular hepatocellular carcinoma (HCC) that shows iso- or hyperintensity (hyperintense HCC) in the hepatobiliary phase (HB phase) of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI).

MATERIALS AND METHODS

We investigated 89 surgically resected cases. Patients were divided into two groups according to the signal intensity in the HB phase of EOB-MRI: hyperintense HCCs (n = 18) and hypointense HCCs (n = 71). We performed immunohistochemical staining for uptake transporter of gadoxetic acid: organic anion transporter polypeptides (OATP8); tumor markers: alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II); hepatic stem cell markers: epithelial cell adhesion molecule (EpCAM), cytokeratin 19 (CK19), and neural cell adhesion molecule (NCAM); biliary marker: CK7; hepatocyte marker: hepatocyte paraffin 1 (HepPar1); markers of HCC differentiation: glypican-3; signaling: beta-catenin, and the respective grade was semiquantitatively determined.

RESULTS

Histopathologically, hyperintense HCCs showed significantly weaker expression of AFP (p < 0.05), PIVKA-II (p < 0.01), EpCAM (p < 0.005), glypican-3 (p < 0.005) relative to the hypointense HCCs, whereas OATP8 (p < 0.0001), HepPar1 (p < 0.05), and beta-catenin (p < 0.001) were overexpressed in hyperintense HCCs compared with hypointense HCCs.

CONCLUSION

Hyperintense HCC expressed OATP8 and showed a feature of mature hepatocytes with a weak expression of stem cell characteristics immunohistochemically. In addition, this type of HCC demonstrated a weaker expression of the poorer prognosis markers including, AFP, PIVKA-II, EpCAM, CK19, and glypican-3.