Hepatoblastoma is a pediatric malignancy characterized by the uncontrolled 
proliferation of immature hepatocytes (hepatoblasts). This disease is diagnosed 
primarily in children younger than 5 years and is disproportionately observed in 
former premature infants. Cytogenetically, hepatoblastoma is characterized by 
numerical aberrations, as well as unbalanced translocations involving the 
proximal region of chromosome 1q. The NOTCH2 gene has been mapped to this locus, 
and it is well established that the NOTCH gene family is an important regulator 
of several developmental pathways. Specifically, the NOTCH2 protein is known to 
delay hepatoblast maturation during early hepatic organogenesis, and the 
reduction of NOTCH2 expression correlates with the differentiation of 
hepatoblasts into hepatocytes and biliary cells in the developing liver. We 
hypothesized that NOTCH2 is involved in the pathogenesis of hepatoblastoma by 
maintaining a population of undifferentiated hepatoblasts. We studied the 
immunohistochemical expression of NOTCH2 and its isoforms NOTCH1, NOTCH3, and 
NOTCH4 and the NOTCH2 primary ligand JAGGED1 in hepatoblastomas. Compared with 
the normal liver, an increased level of NOTCH2 expression was seen in 22 of 24 
(92%) hepatoblastomas. There was no significant staining for other NOTCH 
isoforms and JAGGED1 in hepatoblastomas. Therefore, we suggest that NOTCH2 
expression and activation, independent of JAGGED1 expression, may contribute to 
the pathogenesis of hepatoblastoma. In the hepatoblastoma sinusoidal 
vasculature, we saw NOTCH3 and NOTCH1 expression. These observations have 
potential implications with regard to therapeutic targeting of the NOTCH 
signaling pathway in hepatoblastomas.