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Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis?
BMC Cancer. 2020 Jan 14; 20(1):34.BC

Abstract

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.

Authors+Show Affiliations

Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel. assafmoore@gmail.com. Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 6997801, Tel Aviv, Israel. assafmoore@gmail.com.Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 6997801, Tel Aviv, Israel.Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel.Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 6997801, Tel Aviv, Israel.Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 6997801, Tel Aviv, Israel. Department of Pathology, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel.Department of Pathology, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel.Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraβe 1, 55131, Mainz, Germany.Tissue Bank and Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraβe 1, 55131, Mainz, Germany.Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel.Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 6997801, Tel Aviv, Israel. Department of surgery B, Beilinson campus, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel.Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 6997801, Tel Aviv, Israel.Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraβe 1, 55131, Mainz, Germany.Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Ze'ev Jabotinsky Rd 39, 4941492, Petah Tikva, Israel. Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 6997801, Tel Aviv, Israel.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31937281

Citation

Moore, Assaf, et al. "Young-onset Gastric Cancer and Epstein-Barr Virus (EBV) - a Major Player in the Pathogenesis?" BMC Cancer, vol. 20, no. 1, 2020, p. 34.
Moore A, Hikri E, Goshen-Lago T, et al. Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis? BMC Cancer. 2020;20(1):34.
Moore, A., Hikri, E., Goshen-Lago, T., Barkan, T., Morgenstern, S., Brook, E., Maderer, A., Roth, W., Gordon, N., Kashtan, H., Brenner, B., Moehler, M., & Aharon, I. B. (2020). Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis? BMC Cancer, 20(1), 34. https://doi.org/10.1186/s12885-020-6517-0
Moore A, et al. Young-onset Gastric Cancer and Epstein-Barr Virus (EBV) - a Major Player in the Pathogenesis. BMC Cancer. 2020 Jan 14;20(1):34. PubMed PMID: 31937281.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis? AU - Moore,Assaf, AU - Hikri,Elad, AU - Goshen-Lago,Tal, AU - Barkan,Tamar, AU - Morgenstern,Sara, AU - Brook,Elena, AU - Maderer,Annett, AU - Roth,Wilfried, AU - Gordon,Noa, AU - Kashtan,Hanoch, AU - Brenner,Baruch, AU - Moehler,Markus, AU - Aharon,Irit Ben, Y1 - 2020/01/14/ PY - 2018/11/23/received PY - 2020/01/06/accepted PY - 2020/1/16/entrez PY - 2020/1/16/pubmed PY - 2020/1/16/medline KW - Epstein-Barr virus (EBV) KW - Gastric cancer KW - MSI KW - PD-L1 KW - Young patients SP - 34 EP - 34 JF - BMC cancer JO - BMC Cancer VL - 20 IS - 1 N2 - 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. SN - 1471-2407 UR - https://www.unboundmedicine.com/medline/citation/31937281/Young-onset_gastric_cancer_and_Epstein-Barr_Virus_(EBV)_-_a_major_player_in_the_pathogenesis L2 - https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-6517-0 DB - PRIME DP - Unbound Medicine ER -
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