Banca de QUALIFICAÇÃO: ÁLIFE DIÊGO LIMA SILVA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : ÁLIFE DIÊGO LIMA SILVA
DATE: 24/11/2023
TIME: 08:30
LOCAL: Faculdade de Medicina - Campus Barbalha
TITLE:

ASSOCIATION OF EPSTEIN-BARR VIRUS (EBV) WITH UTERINE CERVICAL CARCINOMA: TRACKING, CHARACTERIZATION OF THE EXPRESSION PATTERN OF LATENT TRANSCRIPTS AND RELATIONSHIP WITH HUMAN PAPILLOMAVIRUS (HPV)

KEY WORDS:

EBV, HPV, Cervical lesions, Cervical carcinoma, RNA-EBER, BamHI-W.

PAGES: 133
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Cervical cancer is the fourth most common malignancy among women worldwide. In Brazil, excluding cases of non-melanoma skin cancer, cervical carcinoma is the third most common type of cancer among women. Epidemiological studies have demonstrated the presence of Epstein-Barr virus (EBV) in cervical cancer samples, indicating a possible association between its infection and the development of this neoplasm. In this context, the present study aimed to determine the presence of EBV in cervical carcinomas and pre-malignant lesions and its association with the Human Papillomavirus (HPV), in addition to determining EBV viral load in infected cases, correlating with the clinicopathological characteristics, investigating the expression pattern of latent genes, and comparing the results of in situ hybridization for EBER RNA and viral DNA, and evaluating the occurrence of a 30bp deletion in the LMP1 gene. Methodology: Eighty-eight samples of carcinoma, product of hysterectomy, were included in this study, 41 from the São Vicente de Paulo Hospital and Maternity and 47 cases from the Tumor Biobank of the Ceará Cancer Institute - ICC. Also, 40 biopsy samples from outpatients were also included, 10 of which were non-neoplastic tissues, serving as controls, 23 low-grade squamous intraepithelial lesions (LSIL) and 7 high-grade (HSIL). To detect EBV, these cases were subjected to polymerase chain reaction (PCR), quantitative PCR (qPCR) to determine viral load, immunohistochemistry (IHC) and in situ hybridization (ISH). HPV16 and HPV18 were also detected by PCR. Results: The prevalence of EBV by PCR was 29.5% in the tumor samples, among them, 46.6% were co-infected with HPV16 and 6.8% with HPV18. Among non-neoplastic lesions, 10% were positive for EBV, 10% were co-infected with HPV16. There was no co-infection with HPV18. There was no statistical significance for the presence of EBV in carcinomas and non-neoplastic lesions (p=0.761 and p=0.911, respectively). The 30bp deletion of the LMP1 gene was found in 57.7% of carcinomas and in 25% of non-neoplastic lesions (OR=4.09). In qPCR analysis, 90.9% of poorly differentiated tumors were EBV positive. The correlation of mean viral load with tumor differentiation and staging revealed statistical significance with p=0.008 and p=0.002, respectively, demonstrating the highest loads in poorly differentiated tumors, stages I and II, as well as in carcinomas classified as LAAC (p=0.074). In carcinoma samples, 12.5% were ISH-EBER positive, 15.9% were positive by IHC for EBNA1, 6.8% for EBNA2 and 17% and 12.5% were positive for LMP1 and LMP2, respectively. The ISH-DNA approach revealed that 50% of the carcinomas analyzed were EBV positive. Conclusions: The study participants demonstrated a remarkable prevalence of EBV, with progressively higher rates depending on the grade of the injury. Some of the samples were infected by strains carrying a 30bp deletion of the LMP1 gene, which demonstrated greater virulence. The latent pattern determined by the analysis of the expression of EBER RNAs and viral proteins resembles latency state III or may even suggest a latent state in which EBER RNA is not expressed. EBV positivity was reinforced by the presence of viral proteins in infiltrating lymphocytes and fibroblasts. Comparison of the ISH-EBER and ISH-DNA techniques showed that the sensitivity for viral detection was greater with the DNA target.

COMMITTEE MEMBERS:
Externo ao Programa - 1353800 - CLAUDIO GLEIDISTON LIMA DA SILVA - nullInterno - HEBERTY DI TARSO FERNANDES FACUNDO
Presidente - MARCOS ANTONIO PEREIRA DE LIMA