Expression of Notch1, Jagged1 and β-catenin and their clinicopathological significance in hepatocellular carcinoma
Abstract:
The Notch/Jagged signaling pathway is important for cellular differentiation and proliferation. Notch1/Jagged1 can either suppress or promote tumors depending on the cell type and context. β-catenin, one of the mediators of the Wnt signalling pathway, represents a key element in one of the most important pathways of carcinogenesis. The aim of this study was to examine the expression of Notch1/Jagged1 and β-catenin in hepatocellular carcinoma and to assign clinicopathological correlations. Immunohistochemical detection of Notch1/Jagged1 and β-catenin was performed in tissue microarrays including 339 Hepatocellular carcinomas, 174 adjacent non-tumor livers and 94 normal livers. The results showed that the rate of expression was 66%, 98% and 97% for Notch1 and 36%, 85% and 92% for Jagged1 respectively in hepatocellular carcinoma, adjacent non-tumor liver and normal liver. Decreased expression of Notch1/Jagged1 was correlated significantly with Edmondson-Steiner grade. However, nuclear β-catenin was expressed in 37% of hepatocellular carcinoma tissue, which was significantly higher than its non-tumor counterparts. Increased nuclear β-catenin expression was correlated with HBs-Ag status and Edmondson-Steiner grade. Moreover, The positive expression of Notch1 was parallel with Jagged1 expression (r =0.235, p=0.000) and reduced Notch1 expression was associated with increased β-catenin expression in hepatocellular carcinoma (r =-0.125, p =0.023). In conclusion, Notch1/Jagged1 were frequently low expressed in hepatocellular carcinoma and correlated with the high expression of β-catenin suggesting that downregulation of Notch1/Jagged1 signaling may sustain tumor progression.