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Department of Endocrinology and Metabolism, Section of Endocrinology (A.V., R.E., A.P.), and Department of Oncology, Section of Pathology (P.F., F.B.), University of Pisa School of Medicine, 56100 Pisa, Italy; Department of Internal Medicine, Section of Sciences, Endocrino-metabolics, and Biochemistry (F.Pa.), University of Siena School of Medicine, 53100 Siena, Italy; Institute of Histology and General Embryology, University of Bologna School of Medicine (F.Pe.), 40126 Bologna, Italy; and Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara School of Medicine and Center of Biotechnology (F.M., L.I., M.T.), 44100 Ferrara, Italy
Address all correspondence and requests for reprints to: Mauro Tognon, Ph.D., Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara School of Medicine, Via Fossato di Mortara 64/B, 44100 Ferrara, Italy. E-mail: tgm{at}unife.it.
Simian virus 40 (SV40) sequences were investigated in human thyroid tumors of different histotypes, Graves disease thyroid specimens, normal thyroid tissues, and peripheral blood mononuclear cells (PBMC) of healthy donors. Specific SV40 large T antigen (Tag) sequences were detected, by PCR and filter hybridization, in human thyroid tumors with a frequency ranging from 66% in papillary thyroid carcinomas (PTC) to 100% in anaplastic thyroid carcinomas (ATC). SV40 was revealed in 60% and 100% of normal thyroid tissues adjacent to PTC and ATC, respectively, but in only 10% of control normal thyroid tissues (NTT) from patients affected by multinodular goiter. Thyroid tissues from patients affected by the Graves disease were found to be SV40 positive with a frequency of 20%. In agreement with previous investigations, the presence of SV40 sequences was detected in 25% of PBMC of healthy individuals. SV40 Tag mRNA was detected by RT-PCR, whereas the viral oncoprotein was revealed by immunohistochemistry with a specific monoclonal antibody. The high prevalence of SV40 footprints in human thyroid tumors indicates that the oncogenic virus may participate as a cofactor in the onset/progression of specific human thyroid cancers. Detection of SV40 sequences in NTT adjacent to thyroid cancers suggests that the viral infection may spread from transformed cells to normal cells surrounding the tumor. The presence of the SV40 footprint in PBMC implies that blood cells are vectors of the virus in other tissues of the host.
This work was supported in part by Associazione Italiana per la Ricerca sul Cancro (to M.T.), Istituto Superiore di Sanità, AIDS Projects (to M.T.), MIUR PRIN and Local Projects (to M.T.), and Consiglio Nazionale delle Ricerche Target Project Biotechnology 2 (to M.T.).
L.I. was the recipient of a fellowship from the Fondazione Cassa di Risparmio di Cento.
Abbreviations: ATC, Anaplastic thyroid carcinoma; GD, Graves disease; mab, monoclonal antibody; MTC, medullary thyroid cancer; NTT, normal thyroid tissue; PBMC, peripheral blood mononuclear cells; PTC, papillary thyroid carcinoma; RXR
, retinoid X receptor-
; SV40, simian virus 40; Tag, large T antigen; TR
1, thyroid hormone receptor-
1.
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