Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma

Abstract

Background The pathogenesis and clinicopathologic characteristics of Epstein-Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC. Methods Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases. Results EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV-negative LELC had significantly shorter overall, disease-specific, and recurrencefree survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBVnegative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases. Conclusions EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV-positive LELC.

Subtraction of Epstein–Barr virus and microsatellite instability genotypes from the Lauren histotypes: Combined molecular and histologic subtyping with clinicopathological and prognostic significance validated in a cohort of 1,248 cases

“…In GC, LELC is a rare variant (1-4%), but over 80% of cases are associated with clonal EBV infection. 8,21 The indolent outcome in EBV-associated LELC possibly results from the brisk host immune response. 22,23 Intriguingly, EBV-associated non-LELC was still a favorable prognostic factor in multivariate analysis (HR 0.587, 95% CI 0.405-0.851, p = 0.005) although it had a poor overall survival rate similar to that of all the D/M cases.…”

“…LELC is a unique histologic type that occurs in a wide variety of locations, namely, the nasopharynx, stomach, lung, thymus, etc. In GC, LELC is a rare variant (1–4%), but over 80% of cases are associated with clonal EBV infection . The indolent outcome in EBV‐associated LELC possibly results from the brisk host immune response .…”

Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability

“…For MSI analysis, we performed multiplex polymerase chain reaction (PCR) with five quasi-monomorphic mononucleotide repeat markers as previously described [55]. Briefly, genomic DNA was isolated from formalin-fixed, paraffin-embedded (FFPE) tumor samples with a QIAamp DNA mini kit (Qiagen, Valencia, CA, USA).…”

Bridging genomics and phenomics of gastric carcinoma

“…For microsatellite instability (MSI) analysis, we performed multiplex polymerase chain reaction (PCR) with five quasimonomorphic mononucleotide repeat markers as previously described. 27 Briefly, genomic DNA was isolated from FFPE tumor samples with a QIAamp DNA mini kit (Qiagen) under a microscope. Each sense primer was end-labeled with one of the fluorescent markers FAM, HEX, or NED.…”