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The acquisition or reactivation of Epstein-Barr virus (EBV) after allogeneic Hematopoietic Stem Cell Transplant (HSCT) can be associated with complications including the development of post-transplant lymphoproliferative disorder (PTLD), which is associated with significant morbidity and mortality. A number of risk factors for PTLD have been defined, including T-cell depletion, and approaches to monitoring EBV, especially in high-risk patients, with the use of preemptive therapy upon viral activation have been described. Newer therapies for the preemption or treatment of PTLD, such as EBV-specific cytotoxic T-cells, hold promise. Further studies to help define risks, diagnosis, and treatment of EBV-related complications are needed in this at-risk population.

BACKGROUND AND OBJECTIVE: Prior Epstein-Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antigen (HLA) and non-HLA variants and childhood EBV infection as it may provide mechanistic insights into EBV-associated MS. METHODS: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. Participants were categorized as seropositive and seronegative for EBV-viral capsid antigen (VCA). The association between prior EBV infection and having POMS was estimated with logistic regression. Interactions between EBV serostatus, major HLA MS risk factors, and non-HLA POMS risk variants associated with response to EBV infection were also evaluated with logistic regression. Models were adjusted for sex, age, genetic ancestry, and the mothers education. Additive interactions were calculated using relative risk due to interaction (RERI) and attributable proportions (APs). RESULTS: A total of 473 POMS cases and 702 controls contributed to the analyses. Anti-VCA seropositivity was significantly higher in POMS cases compared to controls (94.6% vs 60.7%, p

The Epstein–Barr virus (EBV) nuclear antigen leader protein (EBNALP) is essential for the immortalization of naive B lymphocytes (NBLs). However, the mechanisms remain elusive. To understand EBNALP's role in B-cell transformation, we compare NBLs infected with wild-type EBV and an EBNALP-null mutant EBV using multi-omics techniques. EBNALP inactivation alters enhancer–promoter interactions, resulting in decreased CCND2 and increased CASP1 and BCL2L11 expression. Mechanistically, EBNALP interacts with and colocalizes with the looping factor YY1. Depletion of EBNALP reduces YY1 DNA-binding and enhancer–promoter interactions, similar to effects observed with YY1 depletion. Furthermore, EBNALP colocalizes with DPF2, a protein that binds to H3K14ac and H4K16ac. CRISPR depletion of DPF2 reduces both EBNALP and YY1 DNA binding, suggesting that the DPF2/EBNALP complex may tether YY1 to DNA to increase enhancer–promoter interactions. EBNALP inactivation also increases enhancer–promoter interactions at the CASP1 and BCL2L11 loci, along with elevated DPF2 and YY1 binding and DNA accessibility. Our data suggest that EBNALP regulates YY1 to rewire the host genome, which might facilitate naive B-cell transformation. Synopsis: EBNALP alters looping factor YY1 DNA binding and 3D genome organization which might facilitate cell cycle progression and prevent cell death. EBNALP is tethered to DNA by DPF2. EBNALP recruits YY1 to the CCND2 locus and increases enhancer-promoter interaction and gene expression. EBNALP reduces DNA accessibility and limits YY1 DNA binding at the BCL2L11 locus, reducing enhancer-promoter looping and gene expression. EBNALP alters looping factor YY1 DNA binding and 3D genome organization which might facilitate cell cycle progression and prevent cell death. [ABSTRACT FROM AUTHOR]

Background and aim: Extranodal NK/T-cell lymphoma (ENKTL) is a rare and aggressive subtype of non-Hodgkin's lymphoma that most commonly affects the nasal cavity and nasopharynx. The lung is a rare site for ENKTL involvement, and its clinical behavior and prognostic factors are not well understood. This study aimed to analyze survival outcomes and identify prognostic factors in patients with primary lung ENKTL. Methods: A retrospective analysis was conducted using data from 20 cases of primary lung ENKTL, including four patients who were treated at Peking University Third Hospital in Beijing and 16 patients were extracted from the Surveillance, Epidemiology, and End Results Program database. Clinical characteristics, treatment modalities, and survival data were collected and analyzed using Kaplan–Meier and Cox regression models to identify potential prognostic factors. Results: The study cohort included 13 male (65%) and 7 female (35%) patients with a median age of 57 years. Sex was a significant predictor of survival (P = 0.030), with female patients having lower survival rates. Other factors, including age, race, and disease stage, were not significantly associated with survival. Most patients received chemotherapy (45%) or a combination of chemotherapy and radiotherapy (5%), but treatment data were incomplete for 40% of the cohort. The median overall survival was poor, reflecting the aggressive nature of primary lung ENKTL. Conclusions: Primary lung ENKTL is a rare, aggressive malignancy with limited available data. In this cohort, sex was a significant prognostic factor, while other demographic and clinical variables did not show significant associations with survival. Future research should focus on understanding the molecular and immunological drivers of this disease, with an emphasis on discovering novel therapeutic approaches. Large-scale multicenter studies are needed to improve diagnostic and treatment strategies for primary lung ENKTL. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease in which inflammatory responses to exogenic stressors, such as viral infections, has been recognised. The role of viruses in CRSwNP pathogenesis is unclear. Aims/objectives: We aimed to characterise Epstein-Barr virus (EBV), human papillomavirus (HPV), human cytomegalovirus (HCMV), and human adenovirus (HAdV) in nasal polyps and adjacent paired healthy turbinate mucosa. Materials and methods: We used real-time PCR for EBV, HCMV, and HAdV DNA detection, combined PCR/microarrays for HPV detection and genotyping, in samples from 45 patients with CRSwNP. Additionally, we used EBER in situ hybridisation for EBV detection. Results: EBV detection with EBER-ISH was significantly higher in polyps (36%) versus turbinate mucosa (12%). None of the viral comparisons with PCR between polyps and turbinate mucosa for EBV-, HCMV- or HAdV-DNA showed statistically significant differences. All samples were HPV negative. Conclusions and significance: We report higher expression of EBV in nasal polyps (36%) than in adjacent healthy turbinate mucosa (12%), using a valid method; EBER-ISH in 45 patients with CRSwNP. EBV might be a possible stressor that can trigger polypoid inflammation. [ABSTRACT FROM AUTHOR]

Purpose: To explore the potential risk factors for the occurrence of human cytomegalovirus (HCMV) retinitis (CMVR) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Methods: This is a retrospective, nested case-control study conducted in hematological patients with CMVR who underwent allo-HSCT. Patients diagnosed with CMVR after allo-HSCT were included as the case group, and those without CMVR were matched by a ratio of 1:2 and were recruited as controls. We selected 19 pre- and post-transplant indicators for univariate analysis between the cases and controls, and then Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) for exploration of risk factors of the CMVR occurrence. Results: A total of 1308 allo-HSCT patients from January 1, 2020 to July 31, 2023 were analyzed, and 27 patients were diagnosed CMVR with a median onset time of 222 days after transplantation. In univariate analysis, donors of stem cells source, HLA-match types (including matched sibling donor, haploidentical donor, and unrelated donor), post-transplant Epstein-Barr virus (EBV) viremia, platelet implantation time, and serostatus of CMV-IgG were more easily to develop CMVR than controls (p < 0.001, p = 0.003, p < 0.001, p = 0.032, p = 0.038, respectively). Multivariate logistic regression analysis showed that stem cells source (OR 7.823, 95% CI 1.759-34.800), HLA-match types (OR 7.452, 95% CI 1.099-50.542), and post-transplant EBV infection (OR 7.510, 95% CI 1.903-29.640) were positively associated with the onset of CMVR. Conclusion: Stem cells derived from bone marrow and peripheral blood, HLA-match types, and post-transplant EBV viremia are important risk predictors of CMVR in allo-HSCT patients. These results suggest that clinicians should pay more attention to these indicators when formulating preventive measures pre- and post-transplant. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) can cause lymphoproliferative disorders (PTLD) in immunodeficiency individuals. The pathogenesis of EBV infection depends on its effective recognition and elimination. Our study investigated the effect of peripheral lymphocyte subsets (PLS) on the elimination of EBV. A retrospective single-center study included 63 patients with 17 pediatric liver transplant recipients with EBV-induced PTLD (PTLD group) and 46 patients diagnosed with EBV-induced mononucleosis (IM group). Dynamic monitoring of PLS with EBV-DNA loads was performed. EBV-DNA replicated at a high level (5.2E3∼5.93E7 copies/mL in PBMC) before treatment in all patients in PTLD group. B lymphocytes were the main infected cells. After treatment with Rituximab, the EBV-DNA loads decreased below the lower limit of detection in 10 patients (PTLD-stable disease, PTLD-SD group), and the viral loads replicated at lower level in six patients (PTLD-partial response, PTLD-PR group). In the PTLD-SD group, the percentage of CD3+CD8+ T lymphocytes increased beyond the normal range with the ascending of EBV-DNA loads, then it decreased to the normal range accompanied by the clearance of EBV. In the PTLD-PR group, the CD3+CD8+ T lymphocytes kept in the normal range, while the EBV kept on replication. The increased number of CD3+CD8+ T lymphocytes occurred in parallel with the decline in EBV-DNA loads, which is the most useful index in estimating the host capacity of immuno-surveillance against EBV. [ABSTRACT FROM AUTHOR]

Introduction: Infectious agents have been associated with a variety of conjunctival tumors, including lymphoma, ocular surface squamous neoplasia (OSSN), papilloma, and Kaposi sarcoma. Areas covered: We discuss the infectious etiologies of certain conjunctival tumors including conjunctival lymphoma (Chlamydia spp. Helicobacter pylori, Epstein–Barr virus, hepatitis C virus), OSSN (human papillomavirus, human immunodeficiency virus), papilloma (human papilloma virus), and Kaposi sarcoma (Kaposi sarcoma herpesvirus). Their respective oncogenic mechanisms, diagnosis, and treatment options are reviewed. Expert opinion: It is important for the clinician to recognize when tumors of the conjunctiva may be infection-associated. A detailed history and exam are the most important first step in diagnosis; this may be supplemented by tools such as high-resolution optical coherence tomography. For some tumors, the specific causative agent may influence treatment options and outcomes. For others, data suggest the infectious agent does not influence treatment or outcomes, but it is important nonetheless to be aware as further research on these tumors continues. Additionally, there is exciting research investigating novel and minimally invasive diagnostic and treatment options for conjunctival tumors, including treatments that target the infectious agent directly. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a wide range of clinical presentations and is sometimes life-threatening. It is often treated with systemic corticosteroids and etoposide, but no optimal treatment has been identified. Dexamethasone palmitate (DP) contains a combination of dexamethasone and a lipid emulsion and is selectively taken up by activated macrophages. Recently, a small case series reported the efficacy of dexamethasone palmitate (DP) in HLH. Here, we present the results of a nationwide survey in Japan detailing 14 cases of EBV-HLH treated with DP in children. One week after DP initiation, fever, cytopenia, and splenomegaly resolved in 77%, 38%, and 77% of patients (10, 5, and 10 of 13 patients, 1 missing). A 50% or greater reduction in ferritin levels was observed in 62% of patients (8 of 13 patients, 1 missing). In addition, the attending physician judged DP to be effective or partially effective in 12/14 (86%) patients. DP-related adverse events were uncommon, with only two infectious events reported. Thus, DP can be a therapeutic option for EBV-HLH. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV), the first human oncovirus discovered in 1964, has become a focal point in virology, immunology, and oncology because of its unique biological characteristics and significant role in human diseases. As we commemorate the 60th anniversary of EBV's discovery, it is an opportune moment to reflect on the major advancements in our understanding of this complex virus. In this review, we highlight key milestones in EBV research, including its virion structure and life cycle, interactions with the host immune system, association with EBV-associated diseases, and targeted intervention strategies. [ABSTRACT FROM AUTHOR]

Burkitt lymphoma (BL) has a tight association with Epstein–Barr virus (EBV), especially in sub‐Saharan Africa. While the relationship between BL and EBV is well documented, the relationship between the anti‐EBV adaptive immune response, particularly in sub‐Saharan African cases, and disease course, has not been substantially investigated. An analysis of T‐cell receptor (TCR) complementarity determining region‐3 (CDR3) sequences, reported here, from EBV‐positive, Ugandan BL tumor samples revealed a correlation between the presence of anti‐EBV CDR3s and improved overall survival probabilities. Furthermore, chemical complementarity assessments demonstrated higher complementarity for TCR CDR3s and EBV epitopes in the cases where there had been a detection of the anti‐EBV CDR3 AA sequence matches in the BL tumor samples. Overall, the results reported here raise the question of whether EBV targeted immunotherapy would lead to better BL outcomes? [ABSTRACT FROM AUTHOR]

The Epstein–Barr virus (EBV), the first identified human tumour virus, infects over 95% of the individuals globally and has the potential to induce different types of cancers. It is increasingly recognised that EBV infection not only alters cellular metabolism, contributing to neoplastic transformation, but also utilises several non‐cell autonomous mechanisms to shape the metabolic milieu in the tumour microenvironment (TME) and its constituent stromal and immune cells. In this review, we explore how EBV modulates metabolism to shape the interactions between cancer cells, stromal cells, and immune cells within a hypoxic and acidic TME. We highlight how metabolites resulting from EBV infection act as paracrine factors to regulate the TME, and how targeting them can disrupt barriers to immunotherapy. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) infects nearly 90% of adults globally and is linked to over 200,000 annual cancer cases. Immunocompromised individuals from conditions such as primary immune disorders, HIV, or posttransplant immunosuppressive therapies are particularly vulnerable because of EBV's transformative capability. EBV remodels B cell metabolism to support energy, biosynthetic precursors, and redox equivalents necessary for transformation. Most EBV-driven metabolic pathways center on mitochondria. However, how EBV regulates B cell mitochondrial function and metabolic fluxes remains unclear. Here, we show that EBV boosts cardiolipin (CL) biosynthesis, essential for mitochondrial cristae biogenesis, via EBV nuclear antigen 2/MYC-induced CL enzyme transactivation. Pharmacological and CRISPR genetic analyses underscore the essentiality of CL biosynthesis in EBV-transformed B cells. Metabolomic and isotopic tracing highlight CL's role in sustaining respiration, one-carbon metabolism, and aspartate synthesis. Disrupting CL biosynthesis destabilizes mitochondrial matrix enzymes pivotal to these pathways. We demonstrate EBV-induced CL metabolism as a therapeutic target, offering synthetic lethal strategies against EBV-associated B cell malignancies. [ABSTRACT FROM AUTHOR]

Background: To develop an effective vaccine against Plasmodium vivax, the most widely dispersed human malaria parasite, it is critical to understand how coinfections with other pathogens could impact malaria-specific immune response. A recent conceptual study proposed that Epstein-Barr virus (EBV), a highly prevalent human herpesvirus that establishes lifelong persistent infection, may influence P. vivax antibody responses. Here, it was investigated whether EBV could impact the longevity of humoral immune response to P. vivax. Methodology/principal findings: A 14-year follow-up study was carried out among long-term P. vivax-exposed Amazonian individuals (272, median age 35 years), and included 9 cross-sectional surveys at periods of high and low malaria transmission. The experimental approach focused on monitoring antibodies to the major blood-stage P. vivax vaccine candidate, the Duffy binding protein region II (DBPII-Sal1), including a novel engineered DBPII-based vaccine targeting conserved epitopes (DEKnull-2). In parallel, the status of EBV infection was determined over time by the detection of circulating EBV DNA (EBV-DNAemia) and EBV-specific antibodies to lytic (VCAp18) or latent (EBNA1) antigens. Regardless of the malaria transmission period, the results demonstrated that one or multiple episodes of EBV-DNAemia did not influence the longevity of DBPII immune responses to both strain-specific (Sal-1) or strain-transcending (DEKnull-2) antibodies. Also, the average time in which DBPII-responders lost their antibodies was unrelated to the EBV serostatus. Considering all malaria cases detected during the study, there was a predominance of P. vivax mono-infection (76%), with a positive correlation between malaria infection and EBV-DNAemia. Conclusions/significance: In an immunocompetent P. vivax-exposed adult population neither sporadic episodes of EBV-DNAemia nor antibody responses to lytic/latent EBV antigens influence the longevity of both strain-specific and strain-transcending DBPII immune responses. Further studies should investigate the role of acute P. vivax infection in the activation of EBV replication cycle. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV), an oncogenic gamma-herpesvirus, belongs to group 1 carcinogen and is implicated in various cancers, including gastric cancer. Aurora Kinase A is a major mitotic protein kinase that regulates mitotic progression; overexpression and hyperactivation of AURKA commonly promote genomic instability in many tumours. However, the relationship of functional residues of AURKA and EBV in gastric cancer progression remains unknown. We reveal that AURKA overexpression and EBV infection induce aneuploidy in gastric epithelial cells. The AURKA (S89) N-terminal residue is critical for the centrosome maturation process in EBV-infected gastric epithelial cells. The kinase domain residues T287 and T288 of AURKA are essential for centrosome maturation and bipolar spindle formation in EBV-infected gastric cancer cells. We also show that AURKA 287/288 dm reduces the transcript expression of cell cycle markers involved in mitotic entry in EBV infection. This mutant also enhanced the protein expression of p53 and Rb, which was reduced in EBV infection and decreased the Survivin expression. Further, EBNA1, the latent gene of EBV, stabilises the AURKA in its wild-type form and S89A mutant but unable to stabilise in T287/288A double mutant. These mutants also induce mitotic catastrophe by regulating the apoptosis and autophagy pathway in EBV infection. AURKA287/288 dm also promotes autophagosome formation even in EBV infection. Thus, this study demonstrates that the AURKA kinase domain is essential for its functioning and progression of the oncogenesis of EBV-infected gastric epithelial cells. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionThis multicenter study aimed to investigate the clinical characteristics and factors associated with specific viral pathogens in patients with acute retinal necrosis (ARN).A retrospective multicenter cohort study included ARN patients who underwent aqueous or vitreous polymerase chain reaction (PCR) testing. Multivariable mixed-effects Poisson regression was used to identify factors associated with viral pathogens.A total of 56 patients (65 eyes) with ARN were included, with a mean age was 39.9 ± 23.2 years. Anterior chamber cell showed significant inflammation in 89.2%, while vitreous haze was present in 100%. Multifocal retinitis was found in 92.3% of cases. Among these, 49.2% had diffuse or confluent patterns, 15.4% were circumferential, and 23.1% showed satellite lesions. Additionally, 18.5% were ameboid or scalloped shape, while 9.2% had wedge shapes. Varicella zoster virus (VZV) was the most common pathogen (30.8%), followed by Herpes simplex virus (HSV) (13.8%), Cytomegalovirus (CMV) (10.8%), Epstein-Barr virus (EBV) (9.2%), and human herpesvirus (HHV) (3.0%). Co-infections were observed in 20% of eyes. CMV-related ARN was significantly associated with wedge-shaped retinitis (aRR 4.19) and immunocompromised host (aRR 8.8). Younger age and optic disc edema (aRR 5.41) were correlated with HSV-related ARN.VZV was the predominant viral pathogen, with the increasing prevalence of CMV, EBV, and co-infection. Wedge-shaped retinitis and immunocompromised status were notably associated with CMV-related ARN, findings that may guide antiviral therapy decisions in settings where PCR diagnostics are either unavailable or delayed, ultimately improving visual outcomes. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC), one of the tumours with the highest mortality worldwide, is not a homogeneous disease, showing different features according to location, macroscopic aspect, histotype and molecular alterations. Adenocarcinoma is the most frequent epithelial GC (95%), the remaining 5% comprising rare epithelial tumours with their peculiarities, behaviour and incidence <6 cases/100,000/year. Due to the low number of cases, many aspects must be elucidated in this context. In this narrative review, we highlight the importance of a better understanding of rare GCs to personalize the cures in the light of the precision medicine concept. Our main aim is to translate the scarce evidence from the literature into daily clinical practice, never forgetting that all the clinicians dedicated to rare GCs should encourage such patients' enrolment in clinical trials and promote international collaborations. Hence, we focused on the treatment of the following rare GCs: rare gastric adenocarcinomas (hepatoid adenocarcinoma, medullary carcinoma with lymphoid stroma, Paneth cell carcinoma and Salivary Gland carcinoma); squamous cell carcinoma; adenosquamous carcinoma; neuroendocrine gastric neoplasms; gastroblastoma. [ABSTRACT FROM AUTHOR]

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) caused by pathogenic immunoglobulin G antibodies to myelin oligodendrocyte glycoprotein is a rare demyelinating disease of the central nerve system (CNS). The clinical phenotypes of MOGAD include acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis. At present, the mechanism underlying the disease is unknown. Herein, we report two cases of MOGAD accompanied by Epstein-Barr virus (EBV) infection. Both presented inflammation response in the cerebrospinal fluid (CSF), demonstrating elevated level of cell accounts and protein. EBV genomic sequence was also detected in the CSF samples. The patients recovered substantially after 3 months following a combination treatment with methylprednisolone and immunosuppressive therapy with ofatumumab. These cases provide new insight into the production of MOG-IgG and the possible pathological mechanisms underlying MOGAD. The cases also confirm the association with EBV, a virus that infects human B cells and has been proposed to be a trigger for MOGAD. This is the first report on subcutaneous ofatumumab treatment for MOGAD triggered by EBV, suggesting that this is a potentially valuable therapeutic option. [ABSTRACT FROM AUTHOR]

Few pathogens have historically been subjected to as intense scientific and clinical scrutiny as SARS-CoV-2. The genetic, immunological, and environmental factors influencing disease severity and post-infection clinical outcomes, known as correlates of immunity, remain largely undefined. Clinical outcomes of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to those with life-threatening COVID-19 symptoms. While most infected individuals return to their former health and fitness within a few weeks, some develop debilitating chronic symptoms, referred to as long-COVID. Autoimmune responses have been proposed as one of the factors influencing long-COVID and the severity of SARS-CoV-2 infection. The association between viral infections and autoimmune pathologies is not new. Viruses such as Epstein-Barr virus and cytomegalovirus, among others, have been shown to induce the production of autoantibodies and the onset of autoimmune conditions. Given the extensive literature on SARS-CoV-2, here we review current evidence on SARS-CoV-2-induced autoimmune pathologies, with a focus on autoantibodies. We closely examine mechanisms driving autoantibody production, particularly their connection with disease severity and long-COVID. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) is one of the cancers with the highest morbidity and mortality in the world. Many factors are known that may contribute to the development of this disease. These include infectious agents, among which the Epstein–Barr virus (EBV) and human papillomavirus (HPV) may have potential impacts on the occurrence and course of GC. This study analyzed the prevalence of EBV and HPV in GC, particularly in early-onset gastric cancer (EOGC). Our study confirms previous reports regarding the lack of a significant impact of EBV and HPV infection on the occurrence of all subtypes of GC, as well as highlighting the lack of significant dependence on gender and location of the tumor. Gastric cancer (GC) is one of the most common cancers in the world. It is a multi-factorial disease influenced by both genetic and environmental factors such as diet, obesity, radiation exposure, and infectious agents. Viral infections usually lead to chronic inflammation, which can initiate the development of cancers. To date, only a few studies have been published about Epstein–Barr virus (EBV) and human papillomavirus (HPV) infections in the context of the development of GC. In particular, research on the development of cancer among people under 45 years of age, including the impacts of EBV and HPV, is rare, and clear results have not been obtained. The aim of this study was to analyze the frequency of occurrence of EBV and HPV in GC, particularly in early-onset gastric cancer (EOGC). Tissue material from 135 patients with GC, including 84 men and 51 women, was examined. RT-PCR was performed to detect EBV, and PCR was performed to detect HPV. There were no significant impacts of EBV and HPV infections on any subtype of GC. There was also no statistically significant dependence of gender and location of the tumor on any subtype of GC. Further research on the impacts of infectious agents such as EBV and HPV on GC should be conducted using larger populations. [ABSTRACT FROM AUTHOR]

The human body harbors a vast array of microorganisms. Changes in the microbial ecosystem can potentially lead to diseases, including cancer. Traditionally, research has focused more on the gut microbiota and its influence on cancer. However, with the advancement of sequencing technologies, scholars have discovered that microorganisms within kidney tissues are significant components of tumor tissues. Intratumoral microorganisms may affect tumor growth and development through certain mechanisms, influence the function of immune cells, or impact the effectiveness of chemotherapy or immunotherapy in patients. This paper reviews the latest progress in the research on intratumoral microorganisms in renal cancer (RCa). It summarizes the types and distribution characteristics of these microorganisms, discusses the close association between specific viral infections (such as HPV and EBV) and RCa, and highlights the role of microorganisms in the pathogenesis of RCa. This review provides new perspectives for understanding the pathogenic mechanisms of RCa, thereby offering potential clinical applications. [ABSTRACT FROM AUTHOR]

Aim: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB‐MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM‐SBAs). Methods and Results: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB‐MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM‐SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death‐ligand 1 (PD‐L1) and mismatch repair proteins was performed in both SB‐MCs and NM‐SBAs. SB‐MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein–Barr virus (EBV)‐encoded RNAs by in‐situ hybridization. MLH1 promoter methylation status was evaluated in MLH1‐deficient cases. Eleven SB‐MCs and 149 NM‐SBAs were identified. One (9%) SB‐MC was EBV‐positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB‐MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB‐MCs, both with isolated loss of ARID1A. Compared with NM‐SBAs, SB‐MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD‐L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB‐MC patients compared to NM‐SBA cases (P = 0.02). Conclusion: SB‐MCs represent a distinct histologic subtype, with peculiar features compared to NM‐SBAs, including association with coeliac disease, dMMR, PD‐L1 expression, and better prognosis. [ABSTRACT FROM AUTHOR]