Abstract

BackgroundHepatoblastoma, a leading primary hepatic malignant tumor in children, is originated from primitive hepatic stem cells. We aimed to elucidate the relationships between the histological distribution of β-catenin and hepatic stem cell markers with the clinical outcomes of hepatoblastoma.MethodsImmunohistochemistry was applied to detect β-catenin and hepatic stem cell markers expression in 31 hepatoblastoma tumors. We analyzed the relationship between the stem cell markers and the clinical course of hepatoblastoma.ResultsThirty-one hepatoblastoma patients were diagnosed at a mean age of 2.58 ± 3.78 years, and 7 (22.58%) died. A lack of anticipated decrease in alpha-fetal protein levels after neoadjuvant chemotherapy indicated a higher mortality rate. Nuclear β-catenin expression was significantly associated with membranous epithelial cell adhesion molecule (EpCAM) expression in hepatoblastoma tumor specimens. The co-expression of nuclear β-catenin and membranous EpCAM together with an age at diagnosis ≤1.25 years were predictive of an alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy (P < 0.05). An alpha-fetoprotein level < 1200 ng/mL after neoadjuvant chemotherapy and age at hepatoblastoma diagnosis ≤1.25 years are both predictors of better overall and native liver survival in hepatoblastoma patients.ConclusionsPresence of membranous EpCAM with nuclear β-catenin and younger diagnostic age of hepatoblastoma are predictive of serum alpha-fetoprotein levels drop after chemotherapy. Younger diagnostic age and lower alpha-fetoprotein levels after neoadjuvant chemotherapy and are predictive of better overall and native liver survival in hepatoblastoma patients.

Highlights

  • Hepatoblastoma, a leading primary hepatic malignant tumor in children, is originated from primitive hepatic stem cells

  • Subjects with positive staining of both membranous Epithelial cell adhesion molecule (EpCAM) and nuclear β-catenin were more likely to have an AFP level < 1200 ng/mL after neoadjuvant chemotherapy (Odds ratio, 9; 95% confidence intervals (95% CIs): 1.66–49.12; P = 0.01)

  • Here we demonstrate that an age at diagnosis ≤1.25 years and serum AFP levels

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Summary

Introduction

Hepatoblastoma, a leading primary hepatic malignant tumor in children, is originated from primitive hepatic stem cells. We aimed to elucidate the relationships between the histological distribution of β-catenin and hepatic stem cell markers with the clinical outcomes of hepatoblastoma. Hepatoblastoma is a leading hepatic malignant tumor in young children, and is believed to originate from primitive hepatic stem cells during embryogenesis of the liver. During liver development from the fetus to newborn, the population of liver stem cells decreases gradually under fine-tuned control [1, 6]. Deregulation of this developmental process may contribute to the malignant transformation of these hepatic stem cells and result in hepatoblastoma in young children..

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