Interaction of p53 Mutation and B-Catenin Mutation with CK19 Expression on Early Tumor Recurrence and Prognosis of Hepatocellular Carcinoma.
Jia-Huei Tsai, Yung-Ming Jeng, Rey-Heng Hu, Po-Huang Lee, Hey-Chi Hsu. National Taiwan University Hospital, Taipei, Taiwan; National Taiwan University, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan
Background: Cytokeratin 19 (CK19), a molecular marker of hepatic progenitor cells and cholangiocytes, is not expressed in normal hepatocytes but expressed in hepatocellular carcinomas (HCC). However, its role in HCC progression, especially when interacted with p53 and β-catenin mutations, remained largely unknown.
Design: From January 1983 to December 1997, 210 surgically resected, unifocal, primary HCCs were studied retrospectively. CK19 protein expression was detected by immunohistochemistry while mutations of p53 and β-catenin genes were detected by direct sequencing.
Results: CK19 protein expression was detected in 35.7% (75/210), p53 mutation in 47.2% (83/176) and β-catenin mutation in 14.5% (27/186). The tumor size (p=0.0023), grade (p=0.00093), tumor stage (p<1x10-7), high α-fetoprotein (AFP) (p=0.0004), p53 mutation (p=0.024), absence of β-catenin mutation (p=0.0013), and CK19 expression (p=3x10-5) were markers predictive of early tumor recurrence (ETR). The CK19 expression, stage and ETR were strong indicators of poor prognosis (all p<0.0001). Importantly, combination analysis showed an additive unfavorable prognostic interaction of CK19 expression and p53 mutation. On the contrary, concurrent CK19 expression and β-catenin mutation was rare and CK19 expression abolished the suppression effect of β-catenin mutation on HCC progression.
Conclusions: CK19 expression is associated with more aggressive HCC. CK19 cooperates with p53 mutation toward advanced disease. In contrast, CK19 expression and β-catenin mutation appear to be mutually excluded, and they play dramatic opposite roles in vascular invasion, ETR and prognosis of HCC.
Category: Liver & Pancreas
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 256, Tuesday Morning