SAT-572 Morphological and Molecular Alterations in Thyroid Neoplastic Cells Infected by Epstein-Barr Virus May Be Associated to Tumor Evolution

Abstract

ABSTRACT Title: Morphological and molecular alterations in thyroid neoplastic cells infected by Epstein-Barr virus may be associated to tumor evolution. The Epstein-Barr Virus (EBV) is an ubiquitous human herpes virus and more than 90% of adults, worldwide, have evidence of infection. Since the virus is able to cause a latent and persistent infection, interfering in the metabolism of host cells and triggering a tumorigenic process, it has been considered a human carcinogen by the International Agency for Research on Cancer. EBV has been held responsible for 2% of the malignancies, and is associated to nasopharyngeal carcinoma, gastric cancer, Burkitt’s and Hodgkin’s lymphoma. More recently, our group reported the presence of high EBV viral load in malignant thyroid tumors. Thyroid cancer prevalence has been raising all over the world but its typical evolution is indolent and tumors may even regress. In fact, current guidelines advise small low risk tumors observation without immediate surgical intervention. Looking for the putative clinical role of EBV infection in the evolution of thyroid tumors, we aimed to evaluate the ability of the virus to cause morphological and molecular changes in neoplastic thyroid cell lines TPC-1, BCPAP and 8505C. Viral adaptation for the analysis of the cytopathic effect of the neoplastic thyroid cell lines was performed, followed by viral kinetics of 48 hours for viral load and genes expression analysis of KRAS, NRAS, HRAS and TP53. Comparison of the inoculated cells with non-inoculated control cells showed that all tumor cell lines were permissive to the virus; however, the virus caused cytopathic effect, altering the cell morphology only in the TPC-1 and 8505C. There was hyperexpression of KRAS and NRAS in all cell lines whereas the virus was associated to an initial increase of TP53 that further decreased its expression. We conclude that neoplastic thyroid cell lines are permissive to EBV and that the virus is capable of causing cytopathic effect in both well-differentiated and undifferentiated thyroid cell lines. We also demonstrated that EBV interferes in gene expression in thyroid neoplastic cell lines producing an increase in the expression of the oncogenes KRAS, NRAS and TP53 followed by the loss of expression of the tumor suppressor gene TP53. We suggest that these effects could be related to tumor progression. Keywords: Humam Herpesvirus 4. EBV. Thyroid Cancer. Viral Load. RAS expression.