Expression of claudins in human hepatoblastoma

Background/Aims: Claudins are recently described transmembrane proteins of the tight junctions and might play an essential role in carcinogenesis. We characterized the expression of claudin 1, 2, 3, 4 and 7 in human hepatoblastoma with respect to expressional differences between the fetal and embryonal components.

Material/Methods: Fourteen surgically resected specimen were analysed by immunohistochemistry. Monoclonal mouse antibodies were used to detect claudin 2, 4, PCNA, Ki-67 and beta-catenin, rabbit polyclonal antibodies were utilized to localize claudin 1, 3 and 7 expression. Claudin 1,3,4,7 mRNA expressions were measured by real-time RT-PCR in 3 paraffin-embedded fetal hepatoblastoma samples compared to 3 embryonal hepatoblastoma samples. Relative quantification was utilized using ß-actin as internal control, analysis was made by REST (relative expression software tool).

Results: Immunohistochemistry showed strong staining of claudin 1 and 2 in the fetal components, while embryonal cells showed scattered positivity. Claudin 3 expression was mostly negative, except, some weak apical staining of the acinar structures of the both subtypes. Claudin 4 protein was negative in the tumoör cells. Claudin 7 showed weakly positivity in hepatoblastomas. By real-time PCR claudin 1 and 2 were found significantly upregulated in the fetal cell types compared to embryonal cell types dissected from hepatoblastomas (23-fold; p=0.001, 8.5-fold; p=0.001 respectively). Claudin 3,4,7 did not show significant difference between the fetal and embryonal components.

Conclusion: Our results suggest that claudin 1 and 2 are characteristic markers of differentiation in hepatoblastomas. Our data also indicate an association between the activation of the wnt pathway with the more differentiated phenotype.

The project was supported by grants: NKFP-1/0023/2002, ETT-228/2001, OTKA-T037838