Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author PEREIRA, Marina A. FMUSP-HC
RAMOS, Marcus F. K. P. FMUSP-HC
FARAJ, Sheila F. FMUSP-HC
DIAS, Andre R. FMUSP-HC
YAGI, Osmar K. FMUSP-HC
ZILBERSTEIN, Bruno FMUSP-HC
CECCONELLO, Ivan FMUSP-HC
ALVES, Venancio A. F. FMUSP-HC
MELLO, Evandro S. de FMUSP-HC
RIBEIRO JR., Ulysses FMUSP-HC
dc.date.issued 2018
dc.identifier.citation JOURNAL OF SURGICAL ONCOLOGY, v.117, n.5, Special Issue, p.829-839, 2018
dc.identifier.issn 0022-4790
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/28128
dc.description.abstract Background and ObjectivesGastric 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. MethodsWe 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. ResultsEBV-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. ConclusionEBV-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.
dc.language.iso eng
dc.publisher WILEY
dc.relation.ispartof Journal of Surgical Oncology
dc.rights restrictedAccess
dc.subject Epstein-Barr virus infection; microsatellite instability; molecular targeted therapy; programmed death-ligand 1; stomach neoplasms
dc.subject.other death-ligand 1; molecular classifications; cell infiltration; carnoys solution; mismatch-repair; lymph-nodes; carcinoma; subtypes; adenocarcinoma; protein
dc.title Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer
dc.type article
dc.rights.holder Copyright WILEY
dc.description.conferencedate OCT, 2017
dc.description.conferencelocal Rio de Janeiro, BRAZIL
dc.description.conferencename 13th Brazilian Congress of Surgical Oncology
dc.description.group LIM/14
dc.description.group LIM/35
dc.description.group LIM/37
dc.description.group LIM/38
dc.identifier.doi 10.1002/jso.25022
dc.identifier.pmid 29534305
dc.type.category article; proceedings paper
dc.type.version publishedVersion
hcfmusp.author PEREIRA, Marina A.:HC:ICESP
hcfmusp.author RAMOS, Marcus F. K. P.:HC:ICESP
hcfmusp.author FARAJ, Sheila F.:HC:ICESP
hcfmusp.author DIAS, Andre R.:HC:ICESP
hcfmusp.author YAGI, Osmar K.:HC:ICESP
hcfmusp.author ZILBERSTEIN, Bruno:FM:MGT
hcfmusp.author CECCONELLO, Ivan:FM:MGT
hcfmusp.author ALVES, Venancio A. F.:FM:MPT
hcfmusp.author MELLO, Evandro S. de:FM:MPT
hcfmusp.author RIBEIRO JR., Ulysses:FM:MGT
hcfmusp.origem.id WOS:000434145500002
hcfmusp.origem.id 2-s2.0-85043490291
hcfmusp.publisher.city HOBOKEN
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
dc.identifier.eissn 1096-9098
hcfmusp.citation.scopus 11
hcfmusp.citation.wos 10


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