Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma.

BACKGROUND/PURPOSE: Hepatocellular carcinomas (HCCs) commonly originate from pre-malignant lesions consisting of mature hepatocytes. However, recent studies have suggested that some HCCs emerge from hepatic stem/progenitor cells because stem/progenitor cell markers and cholangiocyte markers are found in these HCCs. At the same time, the expression of stem/progenitor cell markers and cholangiocyte markers may also indicate de-differentiation and transdifferentiation of ordinary HCC cells. This study was performed to help clarify the uncertainty surrounding these HCCs.

METHODS

Sixty-eight surgically resected HCC lesions no larger than 5 cm were studied immunohistochemically using a hepatocyte marker (Hepatocyte), 2 cholangiocyte markers (cytokeratins CK7 and CK19), a marker for mucin (Muc1), and a hepatic stem/progenitor cell marker (C-kit).

RESULTS

Hepatocyte, CK7, CK19, Muc1 and C-kit were positively stained in 68 cases (100%), 51 cases (75.0%), 15 cases (22.1%), 8 cases (11.8%) and 8 cases (11.8%), respectively. In those cases positive for CK7, CK19, Muc1 and C-kit, the positively stained cells formed small foci within a large area of negatively stained cells. Small-sized positive cells suggesting hepatic/stem cell origin were found rarely.

CONCLUSIONS

The positivity of cholangiocyte markers, the stem/progenitor cell marker and mucin production were thought to be due to transdifferentiation of HCC cells rather than malignant transformation of stem/progenitor cells.