Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma: the second report: relationship with tumor size and cell differentiation

Background The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. Methods Ninety‐four HCC lesions no larger than 8 cm from 94 patients were immuno‐histochemically studied using two hepatocyte markers (Hep par 1 and α‐fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c‐Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, < 2.0 cm; S2, 2.0–5.0 cm; S3, 5.0–8.0 cm. The tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. Results The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c‐Kit). Conclusion Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression. Highlight Kumagai and colleagues showed that the positive ratios of cholangiocyte and stem/progenitor cell markers tended to be higher in larger sized and less differentiated hepatocellular carcinoma, indicating that ordinary hepatocellular carcinoma can acquire the characteristics of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression.