John Cunningham virus T-antigen expression in anal carcinoma

Authors

  • Sonia Ramamoorthy MD,

    1. Department of Surgery, University of California, San Diego, California
    2. Moores Comprehensive Cancer Center, University of California, San Diego, California
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  • Bikash Devaraj MD,

    1. Department of Surgery, University of California, San Diego, California
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  • Katsumi Miyai MD, PhD,

    1. Department of Pathology, University of California, San Diego, California
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  • Linda Luo BS,

    1. Department of Surgery, University of California, San Diego, California
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  • Yu-Tsueng Liu PhD,

    1. Moores Comprehensive Cancer Center, University of California, San Diego, California
    2. Department of Medicine, University of California, San Diego, California
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  • C. Richard Boland MD,

    1. Gastrointestinal Cancer Research Laboratory, Baylor University Medical Center, Dallas, Texas
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  • Ajay Goel PhD,

    1. Gastrointestinal Cancer Research Laboratory, Baylor University Medical Center, Dallas, Texas
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  • John M. Carethers MD

    Corresponding author
    1. Moores Comprehensive Cancer Center, University of California, San Diego, California
    2. Department of Medicine, University of California, San Diego, California
    3. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Drive, SPC 5368, Ann Arbor, MI 48109-5368
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    • Fax: (734) 232-3838


  • S.R. and B.D. contributed equally. S.R. acquired samples; S.R., C.R.B., A.G., and J.M.C. were responsible for study design; S.R., B.D., L.L., Y.-T.L., and A.G. performed experiments; S.R., B.D., A.G., and J.M.C. wrote the manuscript; S.R. and J.M.C. obtained funding; KM provided pathological expertise.

Abstract

BACKGROUND:

Anal carcinoma is thought to be driven by human papillomavirus (HPV) infection through interrupting function of cell regulatory proteins such as p53 and pRb. John Cunningham virus (JCV) expresses a T-antigen that causes malignant transformation through development of aneuploidy and interaction with some of the same regulatory proteins as HPV. JCV T-antigen is present in brain, gastric, and colon malignancies, but has not been evaluated in anal cancers. The authors examined a cohort of anal cancers for JCV T-antigen and correlated this with clinicopathologic data.

METHODS:

Archived anal carcinomas were analyzed for JCV T-antigen expression. DNA from tumor and normal tissue was sequenced for JCV with viral copies determined by quantitative polymerase chain reaction and Southern blotting. HPV and microsatellite instability (MSI) status was correlated with JCV T-antigen expression.

RESULTS:

Of 21 cases of anal cancer (mean age 49 years, 38% female), 12 (57%) were in human immunodeficiency virus (HIV)-positive individuals. All 21 cancers expressed JCV T-antigen, including 9 HPV-negative specimens. More JCV copies were present in cancer versus surrounding normal tissue (mean 32.54 copies/μg DNA vs 2.98 copies/μg DNA, P = .0267). There was no correlation between disease stage and viral copies, nor between viral copies and HIV-positive or -negative status (28.7 vs 36.34 copies/μg DNA, respectively, P = .7804). In subset analysis, no association was found between JCV T-antigen expression and HPV or MSI status.

CONCLUSIONS:

Anal carcinomas uniformly express JCV T-antigen and contain more viral copies compared with surrounding normal tissue. JCV and its T-antigen oncogenic protein, presumably through interruption of cell regulatory proteins, may play a role in anal cancer pathogenesis. Cancer 2011. © 2010 American Cancer Society.

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