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• W2914282317 abstract "Introduction: Based on gene expression profile studies, gastric cancer (GC) has recently been categorized into molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instable (MSI) tumors. This tumoral characterization, besides providing more prognostic information, allows the identification of molecular pathways and potential therapeutic targets. In this context, the identification of biomarkers including PD-L1 may be useful for patient stratification and development of personalized therapy. Objective: to evaluate the frequence of EBV, MSI and PD-L1 imunoexpression in GC and its relationship to clinicopathological characteristics and prognosis. Methods: We analyzed specimens from 287 patients with GC who underwent gastrectomy with D2 lymphadenectomy using tissue microarray technique. DNA mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) and PD-L1 expression in tumor cells (PD-L1TU), and in inflammatory infiltrated cells were assessed by immunohistochemistry. EBV was detected by in situ hybridization. Results: EBV(+) and MSI were identified in 10.5% and 27% of GC, respectively. Clinicopathological characteristics associated to EBV infection were: male (p=0.032), proximal location (p < 0.001), undetermined/intestinal Lauren type (p < 0.001), poorly differentiated histology (p=0.043) and severe inflammatory infiltration (p < 0.001). MSI-tumors were associated to older age (p=0.002), distal location (p=0.004), lower frequency of lymph node metastasis (LNM) (p=0.024) and lower stage (p=0.020). PD-L1(+) was seen in 8.8% of cases, with predominance of PD-L1TU (6.3%). The PD-L1TU(+) were associated to indeterminate Lauren type (p < 0.001), poorly differentiated histology (p=0.015) and severe inflammatory infiltration (p=0.010). A robust PD-L1 expression was also observed in EBV(+) GC (p < 0.001) patients. Among PD-L1(+) CG, 50% had EBV(+) and 27% MSI. According to the survival analysis, MSI GC had longer disease-free survival (DFS) (p=0.013). Considering only patients with LNM, CG PD-L1TU(+) had DFS significantly worse than PD-L1(-) (p=0.049). Conclusion: The IHQ profile analysis was able to identify subgroups of GC with different characteristics. MSI phenotype was related to longer SLD, confirming its use as a prognostic marker in GC. In addition, EBV(+) and MSI GC together accounts for nearly 70% of PD-L1(+) tumors. This data suggest that subgroup recognition may alter the indication of targeted therapies and improve the prognostic value of current staging systems.Figure: IHC profile.Figure: DFS IHC and PDL1." @default.
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• W2914282317 date "2017-10-01" @default.
• W2914282317 modified "2023-10-01" @default.
• W2914282317 title "Clinicopathological Characteristics and Prognostic Value of Epstein-Barr Virus-associated Gastric Cancer, Microsatellite Instability and PD-L1 Immunoexpression" @default.
• W2914282317 doi "https://doi.org/10.14309/00000434-201710001-01218" @default.
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