Clinicopathologic implication of hepatic progenitor cell marker expression in hepatoblastoma.
Hepatic progenitor cells (HPCs) are thought to play a role in hepatoblastoma, as hepatoblastomas are characterized by an immature histology and a wide variety of cell lineages. We aimed to investigate the extent of expression of HPCs marker and its clinical implication in hepatoblastoma. We collected 61 hepatoblastomas and 9 childhood hepatocellular carcinomas (HCCs) and performed immunohistochemistry for HPC markers, including cytokeratin 19 (CK19), octamer-binding transcription factor 3/4 (Oct-3/4), epithelial cell adhesion molecule (EpCAM), and delta-like 1 homolog (DLK1). Of the hepatoblastoma samples, 27/61 (44.3%), 21/61 (34.4%), 51/61 (83.6%) and 56/61 (91.8%) exhibited positivity for CK19, Oct-3/4, EpCAM and DLK-1, respectively. For HCCs, the rates of expression were 22.2% (CK19), 77.8% (EpCAM) and 77.8% (DLK-1). Oct-3/4 was not expressed in HCC cells. Hepatoblastomas with a poorly differentiated epithelial component had a higher incidence of CK19 and Oct-3/4 expression than those with a well differentiated epithelial component (p=0.005 and 0.037, respectively). Higher disease stage of hepatoblastoma was correlated with CK19 expression (p=0.043). Oct-3/4-positive hepatoblastomas were associated with short disease-free survival (p=0.035). Both hepatoblastomas and childhood HCCs, therefore, exhibit characteristics of HPCs, and the poor prognosis of patients with Oct-3/4-positive hepatoblastoma suggests that stem-like properties affect hepatoblastoma pathogenicity.
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Woong Jae
WJ
Yun
Eun
E
Shin
Kyoungbun
K
Lee
Hae Yoen
HY
Jung
Soo Hee
SH
Kim
Young-Nyun
YN
Park
Eunsil
E
Yu
Ja-June
JJ
Jang
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D002675:Child, Preschool; D005260:Female; D018197:Hepatoblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor
Hepatic progenitor cells; Hepatoblastoma; Immunohistochemistry; Prognosis