Expression of Notch1, Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma.
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. beta-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 beta-catenin in hepatocellular carcinoma and to assign clinicopathological correlations. Immunohistochemical detection of Notch1/Jagged1 and beta-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 beta-catenin was expressed in 37% of hepatocellular carcinoma tissue, which was significantly higher than its non-tumor counterparts. Increased nuclear beta-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 beta-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 beta-catenin suggesting that downregulation of Notch1/Jagged1 signaling may sustain tumor progression.
Wang
M
M
Department of Pathology, The first Affiliated Hospital, SUN YAT-SEN UNIVERSITY, Guang Zhou City, Guang Dong Province, China.
Xue
L
L
Cao
Q
Q
Lin
Y
Y
Ding
Y
Y
Yang
P
P
Che
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000556:secondary; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D051881:Receptor, Notch1 / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
C495270:CTNNB1 protein, human; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D051176:beta Catenin