BACKGROUND AND OBJECTIVES: Gastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. METHODS: We evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. RESULTS: EBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P = 0.032), proximal location (P < 0.001), undetermined Lauren type (P < 0.001), poorly differentiated histology (P = 0.043) and severe inflammatory infiltrate (P < 0.001). MSI-tumors were associated to older age (P = 0.002), subtotal gastrectomy (P = 0.004), pN0 (P = 0.024) and earlier TNM stage (P = 0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P < 0.001). MSI was associated to better survival outcomes. CONCLUSION: EBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.
BACKGROUND AND OBJECTIVES:Gastric cancer (GC) has recently been categorized in molecular subtypes, which include Epstein-Barr (EBV)-positive and microsatellite instability (MSI) tumors. This distinction may provide prognostic information and identifies therapeutic targets. The aim of this study was to evaluate EBV, MSI, and PD-L1 immunoexpression in GC and its relationship with clinicopathological characteristics and patient's prognosis. METHODS: We evaluated 287 GC patients who underwent D2-gastrectomy through immunohistochemistry for DNA mismatch repair proteins and PD-L1, and in situ hybridization for EBV detection utilizing tissue microarray. RESULTS: EBV-positive and MSI were identified in 10.5% and 27% of the GCs, respectively. EBV positivity was associated to male gender (P = 0.032), proximal location (P < 0.001), undetermined Lauren type (P < 0.001), poorly differentiated histology (P = 0.043) and severe inflammatory infiltrate (P < 0.001). MSI-tumors were associated to older age (P = 0.002), subtotal gastrectomy (P = 0.004), pN0 (P = 0.024) and earlier TNM stage (P = 0.020). PD-L1-positive was seen in 8.8% of cases, with predominant expression in EBV-positive GC (P < 0.001). MSI was associated to better survival outcomes. CONCLUSION: EBV-positive GCs had increased PD-L1 expression, while MSI GC had better survival outcome. EBV and MSI subgroups are distinct GC entities, their recognition is feasible by conventional techniques, and it may help individualize follow-up and guide adjuvant therapy.
Authors: Marina Alessandra Pereira; Marcus Fernando Kodama Pertille Ramos; Andre Roncon Dias; Sheila Friedrich Faraj; Cinthya Dos Santos Cirqueira; Evandro Sobroza de Mello; Bruno Zilberstein; Venancio Avancini Ferreira Alves; Ulysses Ribeiro Journal: Chin J Cancer Res Date: 2018-10 Impact factor: 5.087
Authors: Willemieke P M Dijksterhuis; Rob H A Verhoeven; Sybren L Meijer; Marije Slingerland; Nadia Haj Mohammad; Judith de Vos-Geelen; Laurens V Beerepoot; Theo van Voorthuizen; Geert-Jan Creemers; Martijn G H van Oijen; Hanneke W M van Laarhoven Journal: Gastric Cancer Date: 2020-01-11 Impact factor: 7.370
Authors: Marcus Fernando Kodama Pertille Ramos; Marina Alessandra Pereira; Osmar Kenji Yagi; Andre Roncon Dias; Amir Zeide Charruf; Rodrigo Jose de Oliveira; Evelise Pelegrinelli Zaidan; Bruno Zilberstein; Ulysses Ribeiro-Júnior; Ivan Cecconello Journal: Clinics (Sao Paulo) Date: 2018-12-10 Impact factor: 2.365
Authors: Meike Kohlruss; Bianca Grosser; Marie Krenauer; Julia Slotta-Huspenina; Moritz Jesinghaus; Susanne Blank; Alexander Novotny; Magdalena Reiche; Thomas Schmidt; Liridona Ismani; Alexander Hapfelmeier; Daniel Mathias; Petra Meyer; Matthias M Gaida; Lukas Bauer; Katja Ott; Wilko Weichert; Gisela Keller Journal: J Pathol Clin Res Date: 2019-06-17