Abstract

Wnt/β‐catenin signaling is important in normal liver growth and development where it dictates processes of proliferation, zonation and metabolism. Here we examined pediatric hepatoblastoma (HB), hepatocellular cancer (HCC) and tyrosinemias for expression of β‐catenin, its target Glutamine synthetase (GS) and upstream effector glypican‐3 (GPC3) by immunohistochemistry (IHC). Normal livers displayed membranous β‐catenin, cytoplasmic GS in a single layer of pericentral hepatocytes and no GPC3 expression. 2/9 HCC showed cytoplasmic/nuclear localization, which coincided with increased GS and GPC3. All 10 HB showed strong nuclear and cytoplasmic β‐catenin and increased GPC3, but only 7/10 showed diffuse GS staining. 5/6 livers with tyrosinemia (including 2 with dysplasia and 1 with HCC) showed cytoplasmic β‐catenin, which correlated with diffuse GS and increased GPC3 immunoreactivity. We conclude that significant numbers of HCC, HB and tyrosinemias show aberrant β‐catenin activation, which could be due to increased GPC3, which is known to activate Wnt pathway.

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