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Role of p53 and β-catenin Mutations in Conjunction with CK19 Expression on Early Tumor Recurrence and Prognosis of Hepatocellular Carcinoma

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Cytokeratin 19 (CK19), a molecular marker of hepatic progenitor cells and cholangiocytes, is expressed in hepatocellular carcinomas (HCC), but not in normal hepatocytes. However, role of CK19 in HCC progression, especially when interacted with p53 and β-catenin mutations, remained largely unknown.

Materials and Methods

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 DNA 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 = 4 × 10−7), high α-fetoprotein (p = 0.0004), p53 mutation (p = 0.024), absence of β-catenin mutation (p = 0.0013), and CK19 expression (p = 3 × 10−5) were markers predictive of early tumor recurrence (ETR). 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 towards advanced disease. In contrast, CK19 expression and β-catenin mutation play dramatic opposite roles in vascular invasion, ETR and the prognosis of HCC.

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Conflicts of Interest

There are no potential and real conflicts of interest in the subject of this study.

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Authors and Affiliations

  1. Department of Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 10051, Taiwan

    Ray-Hwang Yuan, Rey-Heng Hu & Po-Huang Lee

  2. Department of Pathology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 10051, Taiwan

    Yung-Ming Jeng, Po-Lin Lai & Hey-Chi Hsu

  3. Department of Surgery, College of Medicine, National Taiwan University, No.1, Jen-Ai Road, Section 1, Taipei, 10051, Taiwan

    Ray-Hwang Yuan, Rey-Heng Hu & Po-Huang Lee

  4. Graduate Institute of Pathology, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Section 1, Taipei, 10051, Taiwan

    Yung-Ming Jeng & Hey-Chi Hsu

  5. Department of Medical Research, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, 10051, Taiwan

    Chia-Chi Cheng

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  1. Ray-Hwang Yuan
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Correspondence to Hey-Chi Hsu.

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Yuan, RH., Jeng, YM., Hu, RH. et al. Role of p53 and β-catenin Mutations in Conjunction with CK19 Expression on Early Tumor Recurrence and Prognosis of Hepatocellular Carcinoma. J Gastrointest Surg 15, 321–329 (2011). https://doi.org/10.1007/s11605-010-1373-x

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  • DOI: https://doi.org/10.1007/s11605-010-1373-x

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