Quantification of glypican 3, β-catenin and claudin-1 protein expression in hepatoblastoma and paediatric hepatocellular carcinoma by colour deconvolution

Aims: To identify an immunohistochemical panel for paediatric malignant epithelial liver tumours. Methods and results: Forty-five hepatoblastomas (HBs), 13 paediatric hepatocellular carcinomas (HCCs) and two hepatocellular malignant neoplasms not otherwise specified (NOS) were chosen for immunohistochemical staining of glypican 3 (GPC3), beta-catenin, claudin-1, delta-like protein (DLK), and forkhead box protein G1 (FOXG1). Immunostaining was quantitatively analysed with NIH IMAGEJ software coupled with colour deconvolution. Different subtypes of HB and HCC showed distinct staining patterns of GPC3, beta-catenin, and claudin-1. Moreover, GPC3, beta-catenin and claudin-1 all showed higher expression in classic HCC and embryonal HB than in fetal HB; GPC3 showed complete negativity in small-cell undifferentiated (SCU) HB and fibrolamellar HCC (FLC); beta-catenin showed the strongest expression in SCU HB but the weakest expression in FLC. A panel of these three immunomarkers was useful for the diagnosis of hepatocellular malignant neoplasms NOS. The expression of DLK and FOXG1 was inconstant among fetal and embryonal HB and classic HCC. Conclusions: A panel of GPC3, beta-catenin and claudin-1 is helpful for differentiating HB subtypes and distinguishing HB from HCC.