Markedly downregulated claudin 2 and claudin 4 expression in human hepatocellular carcinoma

Background: Claudins (1–18) are integral membrane proteins recently identified as components of tight junction strands. Aim: The objective was to characterize the expression of claudin 1–5, 7 in human HCCs and liver metastases compared to corresponding nontumorous and normal liver samples. Material and methods: 12 human HCC and 12 colon metastasis samples were examined by real-time RT-PCR for expression of claudin 1–5 and 7. Relative quantification was utilized using GAPDH as internal control. The HCC samples did not show nuclear staining for beta-catenin indicating activation of the wnt pathway. Results: Claudin 4 in HCCs was found downregulated 38 folds and 30 folds compared to normal livers and metastases, respectively. Claudin 2 showed 24 fold downregulation in comparison to normal liver, however, there was no significant expressional difference to metastases. Claudin 2 was 6.5 fold downregulated in HCCs compared to surrounding nontumorous liver, while 6 fold downregulation was found in HCCs to nontumorous tissue surrounding metastases. Claudin 1 was downregulated 4.7 fold in metastases in comparison to surrounding liver tissue. Claudin 7 did not show pronounced alteration between the primary and metastatic liver tumors and nontumorous parenchyma. Conclusion: Taken together, pronounced downregulation of claudin-2 was found significant between HCCs and normal liver. Further, downregulated expression of claudin-2 was found in HCCs in comparison to non-tumorous parenchyma as well. Therefore claudin 2 might be used for differentiation between primary and metastatic liver tumors. On the other hand claudin-4 expression was markedly downregulated in HCCs contrary to metastases and normal liver. The project was supported by grants: NKFP-1/0023/2002.