© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 4, 267-273,
February 20, 2002
© 2002 Oxford University Press
ARTICLE |
Expression of Human Neurotropic Polyomavirus JCV Late Gene Product Agnoprotein in Human Medulloblastoma
Affiliations of authors: L. Del Valle, J. Gordon, S. Enam, S. Delbue, S. Croul, S. Abraham, S. Radhakrishnan, M. Assimakopoulou, K. Khalili, Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, PA; C. D. Katsetos, Department of Pediatrics, MCP-Hahnemann University, and Department of Pediatrics and Pathology and Laboratory Medicine, St. Christopher's Hospital for Children, Philadelphia.
Correspondence to: Kamel Khalili, Ph.D., Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th St., 015-96, Rm. 203, Philadelphia, PA 19122 (e-mail: kkhalili{at}astro.temple.edu).
Background: The human neurotropic polyomavirus, JCV, contains an open reading frame within the late region of the viral genome that encodes a 71-amino-acid protein, agnoprotein. Because accumulating evidence supports an association between JCV infection and human brain tumors, including medulloblastomas, we assessed the presence of JCV Agno gene sequences and the expression of agnoprotein in a series of 20 well-characterized medulloblastomas. Methods: Formalin-fixed, paraffin-embedded tumor tissue samples were used for Agno gene amplification and for immunohistochemical analysis. Adjacent sections were stained with an antibody to agnoprotein and with antibodies to cellular structural and regulatory proteins, including the JCV early gene product, T antigen. Results: Analysis of amplified DNA from paraffin-embedded samples revealed the presence of the Agno gene in 11 (69%) of 16 samples. Immunohistochemical analysis showed cytoplasmic localization and widespread distribution of agnoprotein in the neoplastic cells in 11 (55%) of 20 samples. The JCV early gene product, T antigen, was present in the nucleus of some, but not all, of the neoplastic cells. Some medulloblastoma samples that expressed agnoprotein had no sign of T-antigen expression. p53 was detected in only six of the 11 tumors in which agnoprotein was expressed. None of the 20 samples showed expression of the viral late capsid proteins, ruling out productive infection of the tumor cells with JCV. Conclusions: Our data provide evidence that the JCV late gene encoding the auxiliary agnoprotein is expressed in tumor cells. The finding of agnoprotein expression in the absence of T-antigen expression suggests a potential role for agnoprotein in pathways involved in the development of JCV-associated medulloblastomas.
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