High-density allelotyping of chromosome 8p in hepatocellular carcinoma and clinicopathologic correlation

Authors

  • Kok-Lung Chan B.Sc.,

    1. Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
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    • This article is being submitted as part of Kok-lung Chan's master's thesis.

  • Joyce Man-Fong Lee M.Sc.,

    1. Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
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  • Xin-Yuan Guan Ph.D.,

    1. Department of Clinical Oncology, University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
    2. Center for the Study of Liver Disease, the University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
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  • Sheung-Tat Fan M.D.,

    1. Department of Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
    2. Center for the Study of Liver Disease, the University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
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  • Irene Oi-Lin Ng M.D.

    Corresponding author
    1. Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
    2. Center for the Study of Liver Disease, the University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China
    • Room 127B, UPB, Department of Pathology, the University of Hong Kong, Queen Mary Hospital, 102, Pokfulam Road, Pokfulam, Hong Kong, People's Republic of China
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    • Fax: 011-44-852-2872-5197


Abstract

BACKGROUND

Allelic deletions are frequent genetic alterations in patients with hepatocellular carcinoma (HCC).

METHODS

To evaluate the allelic losses on chromosome 8p in HCC patients and define their clinicopathologic significance, we performed high-density allelotyping on 8p in 60 patients with HCC and analyzed the clinicopathologic correlation.

RESULTS

Using 24 microsatellite markers, allelic losses on 8p were frequent. Loss of heterozygosity (LOH) at one or more loci was observed in 34 (57%) HCC patients. When the allelic losses were compared between groups categorized by clinicopathologic variables, significant correlation was found between tumors with interstitial losses and larger tumor size (> 5 cm; P = 0.026). In addition, allelic loss at D8S298 at 8p22 was associated closely with venous permeation, tumor microsatellite formation, and larger tumor size (P = 0.019, 0.024, and 0.007, respectively). LOH at locus D8S1721 at 8p23.1 was seen more frequently in nonencapsulated tumors (P = 0.007) and LOH at D8S1771 at 8p21.3 was associated with a larger tumor size and poorer cellular differentiation (P = 0.018 and 0.049, respectively).

CONCLUSIONS

Allelic losses on 8p are frequent in HCC patients. Association of allelic losses at specific loci on 8p with a more aggressive tumor behavior suggests that loss/inactivation of putative tumor suppressor gene(s) located at these regions may confer a tumor growth advantage and contribute to the progression of HCC. Cancer 2002;94:3179–85. © 2002 American Cancer Society.

DOI 10.1002/cncr.10612

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