Outlooks on Epstein-Barr virus associated gastric cancer

Naseem, Madiha; Barzi, Afsaneh; Brezden-Masley, Christine; Puccini, Alberto; Berger, Martin D.; Tokunaga, Ryuma; Battaglin, Francesca; Soni, Shivani; McSkane, Michelle; Zhang, Wu; Lenz, Heinz‐Josef

doi:10.1016/j.ctrv.2018.03.006

Cited by 172 publications

(163 citation statements)

References 86 publications

(162 reference statements)

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“…The frequency of EBV‐positive and MMR‐deficient tumours in our cohort is slightly lower compared to GC cohorts in previous publications, where EBV‐positive tumours occurred in a range of between 4 and 14% and MMR‐deficient tumours between 8 and 26% 5,7‐11,16 . We hypothesise that the observed differences of EBV frequency are due mainly to the different patient populations under study, and reflect the known geographical variation in EBV positivity, with both ethnicity and lifestyle as well as environmental risk factors and coinfections as contributing factors 17 . We exclude intratumoural heterogeneity as a potential source of declaring a case as false negative, as all EBV‐positive cases showed uniform positivity in all TMA tissue cores where tumoral tissue was present.…”

Section: Discussionsupporting

confidence: 91%

Preservation of Epstein–Barr virus status and mismatch repair protein status along the metastatic course of gastric cancer

et al. 2020

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Aims: Epstein-Barr virus (EBV) in-situ hybridisation and mismatch repair (MMR) protein immunohistochemistry identifies two subgroups of gastric cancer (GC) with high immunogenicity and likelihood for response to immune check-point inhibition. As tumour biology may change during the metastatic course, which can negatively influence the success of therapeutic decisions made on primary tissue, we investigated the consistency of GC EBV and MMR status within primary tumours and metastases. Methods and results: We investigated a cohort of 415 primary resected GC, including 111 cases with corresponding distant metastases and 297 cases with lymph node metastases. Tumours were analysed by EBV in-situ hybridisation and MLH1, PMS2, MSH2 and MSH6 immunohistochemistry using tissue microarray technique. Primary tumours were grouped as EBV-positive MMR-proficient, EBV-negative MMR-deficient and EBV-negative MMR-proficient.Eleven of 415 (2.7%) of primary tumours were EBVpositive MMR-proficient, whereas 49 of 415 (11.8%) of tumours were EBV-negative MMR-deficient. EBV and MMR protein status showed full concordance with that of the primary tumours. MMR-deficient tumours were of lower pT-category (P < 0.001), had fewer lymph node metastases [24 of 49 (49%) versus 273 of 361 (75.6%) cases; P < 0.001] and a lower rate of distant metastases [six of 49 (12.2%) versus 105 of 366 (28.7%) cases; P = 0.015]. Conclusion: We demonstrate a strong correlation of EBV and MMR status between primary tumours, lymph node and distant metastases in a large series of primary resected GC. The cases showed the expected frequency of EBV-positive MMR-deficient and EBV-negative MMR-proficient tumours. We conclude that tissue testing for molecular subtyping for therapeutic decision-making can be reliably performed on primary tumours and metastases in GC.

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Section: Discussionsupporting

confidence: 91%

Preservation of Epstein–Barr virus status and mismatch repair protein status along the metastatic course of gastric cancer

et al. 2020

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“…This study suggests that EBV-positive GCs may be good candi-dates for pembrolizumab monotherapy [75]. Another open-label, multi-arm phase II trial (NCT02951091) is testing the efficacy of nivolumab in EBV-positive GCs as second-line treatment [87]. EBV-positive GCs are commonly accompanied by more extensive infiltration of CD8-positive cytotoxic T cells and IFN-γ, which induce expression of IDO, a potent immune cell inhibitor [76,85].…”

Section: Microsatellite Instabilitymentioning

confidence: 89%

“…EBV infection demonstrates four latency patterns depending on combinations of latent gene products during the EBV latency cycle: latency Ia, Ib, II, and III. EBV-positive GC demonstrates the latency I pattern, which is limited to EBV-encoded small RNAs (EBERs), BamHI-A rightward transcripts, and Epstein-Barr nuclear antigen 1 [87,88]. The presence of latent membrane protein (LMP) 2A can distinguish latency type Ia or Ib, and LMP2A is expressed in over 50% of EBV-positive GCs [87].…”

Section: Microsatellite Instabilitymentioning

confidence: 99%

Tumor immune response and immunotherapy in gastric cancer

Kwak

Seo

Lee

et al. 2020

J Pathol Transl Med

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Recent studies have reported the promising results of immunotherapy in many solid tumors [1]. Unlike traditional cancer therapy, which targets the tumor directly, immunotherapy offers a different approach and is an alternative treatment option for patients with cancer. Because immunotherapy generally engages immune reactions to recognize and eliminate tumor cells, demand for understanding the tumor immune response has increased. Resulting from increased study, novel biomarkers associated with the tumor immune reaction have emerged. These biomarkers may allow innovative approaches in patient selection for immunotherapy and lead to advanced treatment response, expanding the potential impact of immunotherapy. After the advent of U.S. Food and Drug Administration (FDA)-approved anti-programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy agents, the importance of immunotherapy in gastric cancer (GC) has continuously increased. In this review article, we recapitulate the general concept of immuno-oncology and discuss its clinical application while focusing on historical and current clinical trials.

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“…EBVassociated gastric cancer (EBVaGC) accounts for about 10% of all GC reported cases [163,164]. The incidence of EBVaGC shows variation in geographical distribution across the globe, with a pooled estimate in Europe, Asia, and North and South America, being 9.2%, 8.3% and 9.9%, respectively (Huang et al, 2014), whereas in Africa, a country like Zambia has a frequency of 23% [165]. EBVaGC is classified into three histological subtypes namely: lymphoepitheliomalike carcinoma (LELC)-type, conventional type adenocarcinoma (CA)-type, and carcinoma Crohn's disease-like lymphoid reaction (CLR)-type [166].…”

Section: Ebv-associated Gastric Cancer (Ebvagc)mentioning

confidence: 99%

Epstein Barr Virus Associated Lymphomas and Epithelia Cancers in Humans

Ayee¹,

Ofori²,

Wright³

et al. 2020

J. Cancer

112

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Epstein Barr virus (EBV) is a cosmopolitan oncogenic virus, infecting about 90% of the world's population and it is associated to tumors originating from both epithelia and hematopoietic cells. Transmission of the virus is mainly through oral secretions; however, transmission through organ transplantation and blood transfusion has been reported. In order to evade immune recognition, EBV establishes latent infection in B lymphocytes where it expresses limited sets of proteins called EBV transcription programs (ETPs), including six nuclear antigens (EBNAs), three latent membrane proteins (LMP), and untranslated RNA called EBV encoded RNA (EBER), shown to efficiently transform B cells into lymphoblastic cells. These programs undergo different patterns of expression which determine the occurrence of distinct types of latency in the pathogenesis of a particular tumor. Hematopoietic cell derived tumors include but not limited to Burkitt's lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and natural killer (NK)/T cell lymphoma. EBV undergoes lytic infection in epithelia cells for amplification of the viral particle for transmission where it expresses lytic stage genes. However, for reasons yet to be unveiled, EBV switches from the expression of lytic stage genes to the expression of ETPs in epithelia cells. The expression of the ETPs lead to the transformation of epithelia cells into permanently proliferating cells, resulting in epithelia cell derived malignancies such as nasopharyngeal cancer, gastric cancer, and breast cancer. In this review, we have summarized the current updates on EBV associated epithelial and B cell-derived malignancies, and the role of EBV latency gene products in the pathogenesis of the cancers, and have suggested areas for future studies when considering therapeutic measures

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Outlooks on Epstein-Barr virus associated gastric cancer

Cited by 172 publications

References 86 publications

Preservation of Epstein–Barr virus status and mismatch repair protein status along the metastatic course of gastric cancer

Preservation of Epstein–Barr virus status and mismatch repair protein status along the metastatic course of gastric cancer

Tumor immune response and immunotherapy in gastric cancer

Epstein Barr Virus Associated Lymphomas and Epithelia Cancers in Humans

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