Preservation of Epstein-Barr-Virus Status and Mismatch Repair Protein Status along the Metastatic Course of Gastric Cancer.

Dislich, Bastian; Blaser, Nicola; Berger, Martin D; Gloor, Beat; Langer, Rupert (2020). Preservation of Epstein-Barr-Virus Status and Mismatch Repair Protein Status along the Metastatic Course of Gastric Cancer. Histopathology, 76(5), pp. 740-747. Wiley 10.1111/his.14059

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(1) Background: EBV in-situ hybridization and mismatch repair (MMR) protein immunohistochemistry identifies two subgroups of gastric cancer (GC) with high immunogenicity and likelihood for response to immune checkpoint inhibition. As tumor 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 tumors and metastases. (2) Patients and Methods: We investigated a cohort of 415 primary resected GC, including 111 cases with corresponding distant metastases and 297 cases with lymph node metastases. Tumors were analyzed by EBV in-situ hybridization and MLH1, PMS2, MSH2, and MSH6 immunohistochemistry using tissue microarray technique. (3) Results: Primary tumors were grouped EBV-positive MMR-proficient, EBV-negative MMR-deficient and EBV-negative MMR-proficient. 11/415 (2.7%) of primary tumors were EBV-positive MMR-proficient whereas 49/415 (11.8%) of tumors were EBV-negative MMR-deficient. EBV and MMR protein status showed full concordance with that of the primary tumors. MMR-deficient tumors were of lower pT-category (p<0.001), had fewer lymph node metastases (24/49 (49%) versus 273/361 (75.6%) cases; p<0.001) and a lower rate of distant metastases (6/49 (12.2%) versus 105/366 (28.7%) cases; p=0.015). (4) Conclusion: We demonstrate a strong correlation of EBV and MMR status between primary tumors, 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 tumors. We conclude that tissue testing for molecular subtyping for therapeutic decision-making can be reliably performed on primary tumors and metastases in GC.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Dislich, Bastian; Blaser, Nicola Andrea; Berger, Martin Dave; Gloor, Beat and Langer, Rupert


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health








Lilian Karin Smith-Wirth

Date Deposited:

23 Jan 2020 14:09

Last Modified:

23 Apr 2020 01:32

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Epstein-Barr virus gastric cancer metastases microsatellite instability mismatch repair molecular subtype




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