Comparison of Clinicopathologic Parameters and Survivals Between Epstein-Barr Virus–positive and Her2-positive Gastric Cancers

Irkkan, Çiğdem; Balcı, Serdar; Tezel, Gaye Güler; Akinci, Bulent; Yalçın, Bülent; Güler, Gülnur

doi:10.1097/pai.0000000000000353

Cited by 14 publications

(8 citation statements)

References 36 publications

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“…One study has found significantly less high HER2 expression in EBV positive cases than in EBV negative (5% versus 24%; p < 0.001) and has suggested that LMP2A may suppress the HER2 expression [20]. Other studies have also found a negative correlation between EBV and HER2 positivity [21,22]. One study has found a slightly higher HER2 expression in EBV positive GC cases (7%) than described in other reports [23].…”

Section: Discussionmentioning

confidence: 90%

Young-onset gastric cancer and Epstein–Barr Virus (EBV) – a major player in the pathogenesis?

et al. 2020

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Objective: Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC. Methods: Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records. Results: Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002). Conclusion: Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.

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Section: Discussionmentioning

confidence: 90%

Young-onset gastric cancer and Epstein–Barr Virus (EBV) – a major player in the pathogenesis?

et al. 2020

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“…In the present study, the estimated EBV positive rate was 11.3%. EBV positive rates ranged from 1.2% to 89.2% in the individual eligible studies [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, EBV positivity has been significantly correlated with some clinicopathological characteristics, sex, and tumor location [ 22 , 26 , 53 ]. In the present study, there was a significant correlation between EBV positivity and the patient’s sex; however, EBV positivity was not correlated with lymphovascular invasion or pTNM stage.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

2020

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Background and objectives: The present study aims to elucidate the clinicopathologic significance of Epstein–Barr virus (EBV) infection in gastric carcinomas (GCs) through a meta-analysis. Materials and Methods: Sixty-one eligible studies were included in the present meta-analysis. The included patients, with and without EBV infection, were 2063 and 17,684, respectively. We investigated the clinicopathologic characteristics and various biomarkers, including programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs). Results: The estimated EBV-infected rate of GCs was 0.113 (95% confidence interval (CI): 0.088–0.143). The EBV infection rates in GC cells were 0.138 (95% CI: 0.096–0.194), 0.103 (95% CI: 0.077–0.137), 0.080 (95% CI: 0.061–0.106), and 0.042 (95% CI: 0.016–0.106) in the population of Asia, America, Europe, and Africa, respectively. There was a significant difference between EBV-infected and noninfected GCs in the male: female ratio, but not other clinicopathological characteristics. EBV infection rates were higher in GC with lymphoid stroma (0.573, 95% CI: 0.428–0.706) than other histologic types of GCs. There were significant differences in high AT-rich interactive domain-containing protein 1A (ARID1A) and PD-L1 expressions, and high CD8+ TILs between EBV-infected and noninfected GCs. Conclusions: Our results showed that EBV infection of GCs was frequently found in male patients and GCs with lymphoid stroma. EBV infection was significantly correlated with ARID1A and PD-L1 expressions and CD8+ TILs in GCs.

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“…It has been reported that there are some histopathological features of ERBB2+ GC ( Park et al, 2016 ). ERBB2 positivity is more often observed in intestinal-type GC ( He et al, 2013 ; Irkkan et al, 2017 ). Up-to-date, there is no correlation analysis on both levels of genomics and clinical histology for ERBB2+ GC.…”

Section: Discussionmentioning

confidence: 99%

Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer

et al. 2018

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Exploring ERBB2-related pathways will help us finding sensitive molecules and potential combined therapeutic targets of ERBB2-targeted therapy for ERBB2+ gastric cancer (GC). In this study, we performed a cross-databases study focused on ERBB2+ GC. The data of ERBB2+ GC deposited in the cancer genome atlas (TCGA), gene expression omnibus (GEO), InBio MapTM, cancer cell line encyclopedia (CCLE), and cancer therapeutics response portal (CTRP) were analyzed. The correlation of expression levels of candidate and IC50 of candidate genes-targeted drugs were verified on NCI-N87 and MKN-45 GC cell lines. We found that RARA, THRA, CACNB1, and TOP2A are drug sensitive biomarkers of ERBB2-targeted treatment with FDA-approved drugs. All these genes act through Myc signaling pathway. Myc is the downstream hub gene of both ERBB2 and RARA. The expression of RARA, THRA, and CACNB1 were negatively correlated with Myc activation, while ERBB2 and TOP2A positively correlated with Myc activation. SH3BGRL3, SH3BGRL, and NRG2 were identified as potential ligands of ERBB2. The ERBB2+ GC with RARA amplification demonstrated better prognosis than those without RARA amplification, while overexpression of NRG2 and SH3BGRL correlated with poor prognosis in ERBB2+ GC. About 90% of ERBB2+ GC was compatible with chromosome instability (CIN) subtype of TCGA, which overlaps with intestinal-type GC in Lauren classification. In validating experiments, combination of Lapatinib and all-trans retinoic acid (ATRA) synergistically suppresses cell growth, and accompanied by decreased expression of MYC. In conclusions, we identified several predicting biomarkers for ERBB2-targeted therapy and corresponding histological features of ERBB2+ GC. Combination of ERBB2 antagonist or RARA agonist may be effective synergistic regimens for ERBB2+ GC.

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Comparison of Clinicopathologic Parameters and Survivals Between Epstein-Barr Virus–positive and Her2-positive Gastric Cancers

Cited by 14 publications

References 36 publications

Young-onset gastric cancer and Epstein–Barr Virus (EBV) – a major player in the pathogenesis?

Young-onset gastric cancer and Epstein–Barr Virus (EBV) – a major player in the pathogenesis?

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer

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