title: Investigation on the association between thyroid tumorigeneses and herpesviruses.
abstract: Herpesviruses have been associated with various human malignancies and with thyroid autoimmunity. Aiming to investigate the presence of these viruses in thyroid nodules, we analyzed serum and thyroid tissue from 183 patients (83 benign and 100 malignant thyroid nodules). We also obtained 104 normal thyroid tissues extracted from the contralateral lobe of these patients. We used ELISA to screen the serology of all patients and a real-time quantitative PCR to analyze thyroid tissue viral load in antibody-positive patients. In addition, the presence of herpesviruses was tested by histological analysis in 20 EBV-positive tissues using the expression of LMP-1 by immunohistochemistry (IHC) and EBER by in situ hybridization (ISH). There was no evidence of HSV-2 or CMV DNA, but we found EBV DNA sequences in 29 (16%) thyroid tissue samples. We also found 7 positive EBV cases out of 104 normal tissues. Viral load was higher in tumors than in their respective normal tissues (p = 0.0002). ISH analysis revealed EBER expression in 11 out of 20 (52%) EBV-positive tissues, mostly in malignant cases (8/11, 73%). The presence of high EBV copy numbers in thyroid tumors and the expression of EBER only in malignant cases suggest an association between EBV and thyroid malignancies. However, we did not find any association between the presence of EBV and/or its viral load and any clinical or pathological tumor feature. Further studies aiming to clarify the mechanisms of EBV infection in thyroid cells are necessary to support a possible role in the development of thyroid cancer.
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: J F M
authors.initials: JFM
authors.lastname: Almeida
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, Taguá Street, 440, Liberdade, São Paulo, SP, 01508-010, Brazil.
authors.forename: A H
authors.initials: AH
authors.lastname: Campos
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Marcello
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: N E
authors.initials: NE
authors.lastname: Bufalo
authors.affiliation: Clinical Pathology Department, Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Vital Brasil Street, 251, Cidade Universitária, Campinas, São Paulo, 13083-888, Brazil.
authors.forename: C L
authors.initials: CL
authors.lastname: Rossi
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: L H P
authors.initials: LHP
authors.lastname: Amaral
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: A B
authors.initials: AB
authors.lastname: Marques
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: L L
authors.initials: LL
authors.lastname: Cunha
authors.affiliation: Laboratory of Pathology, Clinical Pathology Institute (IPC), Av. Orosimbo Maia, 165, Vila Itapura, Campinas, São Paulo, 13023-002, Brazil.
authors.forename: C A
authors.initials: CA
authors.lastname: Alvarenga
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil.
authors.forename: P C
authors.initials: PC
authors.lastname: Tincani
authors.affiliation: Head and Neck Surgery Department, University of Campinas Teaching Hospital (HC-Unicamp), Vital Brasil Street, 251, Cidade Universitária, Campinas, SP, 13083-888, Brazil.
authors.forename: A J
authors.initials: AJ
authors.lastname: Tincani
authors.affiliation: Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Tessália Vieira de Camargo Street, 126, Cidade Universitária, Campinas, São Paulo, 13083-887, Brazil. ward@fcm.unicamp.br.
authors.forename: L S
authors.initials: LS
authors.lastname: Ward
mesh_terms: D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D013961:Thyroid Gland / Q000473:pathology* / Q000821:virology; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000821:virology
chemical_list: D004279:DNA, Viral
keywords: Epstein–Barr virus infection; Herpesvirus; Thyroid cancer.; Thyroid nodules; Viral load