Abstract 5348: Detection of herpes simplex viruses in thyroid cancer

Abstract

Abstract Introduction: There is limited information about the role of herpesviridae viruses in thyroid cancer. Materials and Methods: Thyroid tissues from 109 patients with benign (44) and malignant (65) lesions were analyzed for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression and activation of viral-inducible signaling pathways. Expression of viral entry receptor Nectin-1 was examined in human samples and in cancer cell lines. In vitro experiments were performed to explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV. Results: HSV was detected in 43/109 (39.4%) of examined samples. HSV positive tumors were characterized by interferon-beta expression, nuclear NFkB expression and Akt activation. Lymphocytes infiltration and oncocytic cellular features were common in HSV positive tumors. HSV1 was detected with same frequency in benign and malignant thyroid tumors. HSV2 was significantly associated with papillary thyroid cancer and presence of lymph nodes metastases. Nectin-1 expression was increased in thyroid tumors compared to normal thyroid tissue and further increased in papillary thyroid cancer. The level of Nectin-1 expression in cancer cell lines correlated with their susceptibility to HSV. Inhibition of PI3K/AKT or MAPK/ERK signaling did not affect the level of Nectin-1 expression but decreased thyroid cancer cell susceptibility to HSV. Thyroid cancer cell with epithelial-like morphology underwent epithelial to mesenchymal transition after chronic exposure to TNF. Induction of epithelial to mesenchymal transition was associated with increased thyroid cancer cell susceptibility to HSV. Conclusion. HSV was detected in human thyroid tumors and HSV2 was associated with metastatic thyroid cancers. In vivo and vitro data showed that during tumor progression thyroid cells acquire increased susceptibility to HSV due to 1) increased expression of viral entry mediator Nectin-1; 2) activation of mitogenic signaling and 3) induction of EMT in metastatic cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5348.