Immunohistologic Attempt to Find Carcinogenesis from Hepatic Progenitor Cell in Hepatocellular Carcinoma

Abstract

Aim: To clarify whether hepatocellular carcinoma (HCC) originates from hepatic progenitor cells and whether there is any correlation with the clinicopathologic factors of HCC, we reviewed 217 resected HCC specimens. Methods: Immunohistochemical examination of cytokeratin (CK) 7, CK19, CD34, and CD117 (c-KIT) was performed. Overexpression of CK7 and CK19 indicates differentiation from cholangiocellular and hepatic progenitor cells, while overexpression of CD34 and CD117 indicates hepatic stem cells. Fresh specimens were obtained from 20 HCC patients for mutation of the c-KIT gene. Results: CK7, CK19, and CD117 were positive in 41, 9.7, and 0.9% of the HCC specimens, respectively, and CD34 was never positive. None of the fresh HCC specimens demonstrated a c-KIT mutation. CK19 positivity was significantly correlated with a positive hepatitis B core antibody, and with poor survival outcome, and tended to correlate with poor histologic differentiation. Conclusion: These results suggest that: (i) about 10% of HCCs with typical histologic features originate from an intermediate hepatic progenitor cell, such as the canal of Hering and oval cells in the rat, or acquire the characteristics of cholangiocellular epithelium by metaplasia; (ii) HCC with typical histologic features rarely originates from hepatic stem cells, and (iii) patients with CK19-positive HCC have a poor prognosis.

Cadherin 17 is related to recurrence and poor prognosis of cytokeratin 19‑positive hepatocellular carcinoma

“…However, previous studies also showed that about 10% of HCC with typical microscopic histologic features expressed CK19 (4,6). These CK19(+) HCC was found to behave more aggressively and had a worse outcome (4,(6)(7)(8)17). For example, Takano et al demonstrated that CK19(+) HCC exhibited higher invasiveness, metastatic potential, and poorer prognosis (17).…”

“…Tumor cells from HCC, as a result, should not express CK19 since they are supposed to originate from hepatocytes (16). However, previous studies also showed that about 10% of HCC with typical microscopic histologic features expressed CK19 (4,6). These CK19(+) HCC was found to behave more aggressively and had a worse outcome (4,(6)(7)(8)17).…”

“…CHAO-WEI LEE [1][2][3] , SEY-EN LIN 4 , HSIN-I TSAI 2,3,5 , PO-JUNG SU 2,6,7 , CHIA-HSUN HSIEH 2,6 , YUNG-CHIA KUO 2,3,6 , CHANG-MU SUNG 2,3,8 , CHENG-YU LIN 8 , CHI-NEU TSAI 3 and MING-CHIN YU gene becomes silenced in healthy adult liver and stomach tissues. It functions as a peptide transporter and a cell adhesion molecule to maintain tissue integrity in epithelia (13).…”

“…Studies have shown that the expression of CK19 in primary HCC is associated with poorer outcome (6). There have also been studies demonstrating that CK19 expression in primary HCC is a significant risk factor for developing lymph node metastasis (LNM) (4,7,8).…”

Transplanted bone marrow stromal cells are not cellular origin of hepatocellular carcinomas in a mouse model of carcinogenesis

“…There are increasing evidences that oval cells are the cellular targets for transformation in the development of HCC [7][8] . Oval cells might give rise to HCC as a result of the arrest of stem cell maturation [9] .…”