Clonal origin of multifocal hepatocellular carcinoma

Authors

  • Kurt B. Hodges MD,

    1. Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
    2. Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana
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  • Oscar W. Cummings MD,

    1. Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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  • Romil Saxena MD,

    1. Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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  • Mingsheng Wang MD,

    1. Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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  • Shaobo Zhang MD,

    1. Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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  • Antonio Lopez-Beltran MD, PhD,

    1. Department of Pathology, Cordoba University, Cordoba, Spain
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  • Rodolfo Montironi MD,

    1. Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy
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  • Hammam Nour MS,

    1. Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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  • Liang Cheng MD

    Corresponding author
    1. Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
    • Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, Clarian Pathology Laboratory Room 4010, Indianapolis, IN 46202
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    • Fax: (317) 491-6419


Abstract

BACKGROUND:

Hepatocellular carcinoma is the most common primary tumor of the liver. Patients frequently have multiple histologically similar, but anatomically separate tumors. The clonal origin of multiple hepatocellular carcinomas is uncertain.

METHODS:

The authors analyzed 31 tumors from 12 different patients (11 women, 1 man), who had multiple hepatocellular carcinomas involving 1 or both lobes. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue using laser capture microdissection. DNA was analyzed for loss of heterozygosity (LOH), X chromosome inactivation status, and TP53 gene mutations.

RESULTS:

Ten (83%) of the 12 patients showed LOH in at least 1 of the analyzed microsatellite markers. Concordant LOH patterns between separate hepatocellular carcinomas in individual patients were seen in 8 (80%) of 10 cases, whereas discordant patterns were seen in 2 (20%) of 10 cases. Five (50%) of 10 informative female patients showed identical nonrandom X chromosome inactivation patterns in multiple tumors; 1 case showed discordant nonrandom X chromosome inactivation pattern. TP53 mutations were identified in 8 (67%) of 12 patients. Tumors in 7 (88%) of these 8 patients showed different point mutations. Three patients (Cases 4, 5, and 10) had tumors with additional TP53 point mutations, indicating additional genetic abnormalities in these tumors.

CONCLUSIONS:

The data suggested that the significant proportion of patients with multifocal hepatocellular carcinomas have tumors of common clonal origin. Cancer 2010. © 2010 American Cancer Society.

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