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Ann Oncol. 2016 Mar;27(3):494-501. doi: 10.1093/annonc/mdv610. Epub 2015 Dec 16.

Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer.

Author information

1
Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Cancer Research Institute, Kyungpook National University.
2
Departments of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine.
3
Gastroenterology, Kyungpook National University Hospital, Kyungpook National University School of Medicine.
4
Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine.
5
College of Pharmacy, Institute of Microorganisms and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea.
6
Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Cancer Research Institute, Kyungpook National University jkk21c@knu.ac.kr.

Abstract

BACKGROUND:

This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC).

MATERIALS AND METHODS:

After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above.

RESULTS:

Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio [HR] = 12.193, 95% confidence interval [95% CI] 1.039-143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917-25.525, P = 0.063).

CONCLUSION:

The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.

KEYWORDS:

Epstein–Barr virus-associated gastric cancer; gastric cancer; host immune reaction; prognosis; tumor-infiltrating lymphocytes

PMID:
26673353
DOI:
10.1093/annonc/mdv610
[Indexed for MEDLINE]

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