EBV is a lymphotropic virus, member of the family that asymptomatically infects more than 90% of the human population, establishing a latent infection in memory B cells. EBV exhibits complex survival and persistence dynamics, replicating its genome through the proliferation of infected B cells or production of the lytic virions. Many studies have documented the infection of T/NK cells by EBV in healthy individuals during and after primary infection.
View Article and Find Full Text PDFCommonly attributed to the prevalence of M2 macrophages, tumor-associated macrophages (TAM) are linked to poor outcome in Hodgkin lymphoma (HL). MYC is supposed to control the expression of M2-specific genes in macrophages, and deficiency in MYC-positive macrophages inhibits tumor growth in mouse models. To verify this hypothesis for HL, seventy-six samples were subjected to immunohistochemical double staining using CD68 or CD163 macrophage-specific antibodies and a reagent detecting MYC.
View Article and Find Full Text PDFTo aid understanding of primary EBV infection, we have performed an in depth analysis of EBV-infected cells and of local immune cells in tonsils from infectious mononucleosis (IM) patients. We show that EBV is present in approximately 50% of B-cells showing heterogeneous patterns of latent viral gene expression probably reflecting different stages of infection. While the vast majority of EBV+ cells are B-cells, around 9% express T-cell antigens, with a predominance of CD8+ over CD4+ cells.
View Article and Find Full Text PDFHematol Oncol
October 2018
The search for clinically relevant molecular markers in classical Hodgkin lymphoma (cHL) is hampered by the histopathological complexity of the disease, resulting from the admixture of a small number of neoplastic Hodgkin and Reed-Sternberg (H-RS) cells with an abundant and heterogeneous microenvironment. In this study, we evaluated gene expression profiles of 11 selected genes previously proposed as a molecular score for adult cHL, aiming to validate its application in the pediatric setting. Assays were performed by RT-qPCR from formalin-fixed paraffin-embedded (FFPE) lymph nodes in 80 patients with cHL.
View Article and Find Full Text PDFOncoimmunology
March 2018
Interleukin-10 (IL10) is an immune regulatory cytokine. Single nucleotide polymorphisms (SNPs) in IL10 promoter have been associated with prognosis in adult classical Hodgkin lymphoma (cHL). We analyzed IL10 SNPs -1082 and -592 in respect of therapy response, gene expression and tumor microenvironment (TME) composition in 98 pediatric patients with cHL.
View Article and Find Full Text PDFThe human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models.
View Article and Find Full Text PDFAppl Immunohistochem Mol Morphol
November 2017
Identification of human papillomavirus (HPV) association in head and neck squamous cell carcinoma (HNSCC) is important to identify patients with favorable disease course. However, molecular HPV detection is not universally available. p16 has been proposed as a surrogate marker for HPV infection in HNSCC but, use on its own may result in wrong assignment of some cases to the group of HPV-associated tumors.
View Article and Find Full Text PDFMacrophages have been implicated in the pathogenesis of classical Hodgkin lymphoma (cHL) and have been suggested to have a negative impact on outcome. Most studies addressing the role of macrophages in cHL have relied on identification of macrophages by generic macrophage antigens, e.g.
View Article and Find Full Text PDFThe association of lymphoma with necrotic granuloma can pose diagnostic challenges and delay treatment, especially in settings with a high burden of infection. In these settings, the timely use of cytogenetic and molecular methods is most relevant. Here, we report a case of B-cell lymphoma with t (8;14) in a 5-year-old male child.
View Article and Find Full Text PDFRising prevalence rates of high-risk human papillomaviruses (hrHPV) infection in oropharyngeal carcinoma (up to 80 %) have been reported in North America and Scandinavia. We have analysed 424 German and 163 Brazilian head and neck squamous cell carcinomas (HNSCC) from the oral cavity (OSCC), oropharynx (OPSCC) and hypopharynx (HPSCC) using p16 immunohistochemistry, HPV DNA PCR and sequencing, hrHPV DNA in situ hybridisation (ISH) and hrHPV E6/E7 RNA ISH. In the German series, 52/424 cases (12.
View Article and Find Full Text PDFFormalin-fixed paraffin-embedded (FFPE) tissues are invaluable sources of biological material for research and diagnostic purposes. In this study, we aimed to identify biological and technical variability in RT-qPCR TaqMan® assays performed with FFPE-RNA from lymph nodes of classical Hodgkin lymphoma samples. An ANOVA-nested 6-level design was employed to evaluate BCL2, CASP3, IRF4, LYZ and STAT1 gene expression.
View Article and Find Full Text PDFPrimary infection with the human oncogenic Epstein-Barr virus (EBV) can result in infectious mononucleosis (IM), a self-limiting disease caused by massive lymphocyte expansion that predisposes for the development of distinct EBV-associated lymphomas. Why some individuals experience this symptomatic primary EBV infection, whereas the majority acquires the virus asymptomatically, remains unclear. Using a mouse model with reconstituted human immune system components, we show that depletion of human natural killer (NK) cells enhances IM symptoms and promotes EBV-associated tumorigenesis mainly because of a loss of immune control over lytic EBV infection.
View Article and Find Full Text PDFMacrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses.
View Article and Find Full Text PDFDetecting human papillomavirus (HPV) infection in head and neck squamous cell carcinoma (HNSCC) is clinically relevant, but there is no agreement about the most appropriate methodology. We have studied 64 oropharyngeal carcinomas using p16 immunohistochemistry, HPV DNA in situ hybridisation (ISH) and HPV DNA polymerase chain reaction (PCR) followed by pyrosequencing. We have also evaluated a new assay, RNAscope, designed to detect HPV E6/E7 RNA transcripts.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) is an important environmental factor associated to the development of Burkitt lymphoma (BL) in endemic and intermediate risk regions. However, little is known about the contribution of genetic constitution to the development and clinical response of the disease. The aim of this work was to investigate the role of EBV and Interleukin 10 (IL10) single nucleotide polymorphisms (-1082A/G, -819C/T, -592C/A) and microsatellites (IL10.
View Article and Find Full Text PDFPurpose: Tumor-infiltrating macrophages are associated with adverse outcome in adult classical Hodgkin lymphoma (cHL). We have previously shown age-related changes in the lymphocyte composition of pediatric cHL. We therefore hypothesized that the number, function, and prognostic impact of macrophages in pediatric cHL would be different from adult cases.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) replicates in superficial differentiated cells of oral hairy leukoplakia (OHL). Differentiation of squamous epithelial cells depends on B-lymphocyte-induced maturation protein 1 (Blimp1). Here we show that expression of the EBV immediate-early protein BZLF1 is restricted to Blimp1-positive epithelial cells in OHL.
View Article and Find Full Text PDFClassical Hodgkin lymphoma (cHL) is characterized by a small number of neoplastic cells in a background of reactive cells. Children and adults differ in constitution and functionality of the immune system and it is possible that there may be age-related differences in tumor microenvironment composition in cHL. One hundred children with pediatric cHL were studied.
View Article and Find Full Text PDFEpidemiological patterns established about 20 years ago, divided classical Hodgkin lymphoma (cHL) in three entities with regard to Epstein-Barr virus (EBV) status and histological subtypes and suggested different epidemiological patterns associated with degree of economic development. Here, we investigated histopathological features and EBV association in 100 consecutive pediatric cHL cases occurring in Rio de Janeiro (Brazil). Age at diagnosis ranged from 3 to 18 years (median 14 years) with 27% of cases ≤10 years.
View Article and Find Full Text PDFWe investigated the correlation of tumor characteristics with clinico-biological markers of aggressive disease, evaluated by Ann Arbor stage, risk group, B-symptoms, number of involved anatomic areas, mediastinal mass, nodular sclerosis (NS) grade, and risk, in pediatric Hodgkin lymphoma (HL). Leukopenia and extranodal disease influenced event-free survival (p = 0.032 and p = 0.
View Article and Find Full Text PDFBackground: Polymorphisms in the genes of folate and methionine metabolism enzymes have been associated with some forms of cancer by affecting DNA synthesis, repair, and methylation.
Procedure: A case-control study of 72 retinoblastoma cases and 98 cancer-free children controls was performed to investigate whether the polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), carrier of reduced folate 1 (RFC-1 A80G) and thymidylate synthase (TYMS 2R > 3R) altered the risk for retinoblastoma.
Results: MTR A2756G AG plus GG genotype frequencies were higher in patients than in controls (45% vs.
Objectives: To determine if the number of involved anatomic areas can modify the standard risk groups in pediatric Hodgkin's lymphoma, identifying children who would benefit from a reduction in treatment intensity.
Methods: Retrospective study evaluating age, sex, histology, Ann-Arbor stage, presence of B symptoms, number of involved anatomic areas, risk grouping (favorable vs. unfavorable), and laboratory exams.