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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Dislich_et_al-2020-Histopathology.pdf - Accepted Version Available under License Publisher holds Copyright. Download (15MB) | Preview |
(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.
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