Epstein–Barr virus-associated gastric cancer (EBVaGC) is a distinct molecular subtype, it accounts for up to 10% of all molecular subtypes of gastric cancer (GC). Cells infected with EBV transcribe small non-coding RNAs called EBER. The immune response and tumor microenvironment play an essential role in the progression of EBVaGC.

Our study investigated the involvement of EBV in GC and the specificities of the associated anti-tumor response in Algerian population.

Two cases of GC were selected from a pool of twenty gastrectomies, based on the presence of dense inflammatory infiltrate as a hallmark of EBVaGC. The 50 and 67 year-old patients were in the T3N1 and T3N2 stages respectively. Histological examination revealed a moderately differentiated adenocarcinoma and a moderately differentiated papillary-type adenocarcinoma with lymphoid follicles, respectively, in the two patients.

Chromogenic in situ hybridization (CISH) was EVB⁺ in the second patient. The immunohistochemistry (IHC) indicated a Crohn-Like feature related to EBVaGC, characterised by a strong recruitment of CD79⁺ B Lymphocytes and   CD68⁺ macrophages. The low CD8⁺/CD4⁺ ratio (<1) suggested   a defect of endogenic antigenic presentation in EBV⁺ cells. The low expression of p53 (4.5% vs. 80%) and the over-expression of mTOR (71% vs. 15%) in EBV⁺ patient, in comparison to   EBV^- patient, confirmed a loss of anti-tumor function.

Histological hallmark such as marked   peri-tumoral immune cell infiltration (CD68⁺, CD79⁺, CD4⁺ and CD8⁺) in tumors microenvironment and positivity of EBER in CISH are linked to a favorable prognosis and will be helpful in EBVaGC diagnosis.