Lymphocyte-Rich Gastric Cancer: Associations with Epstein-Barr Virus, Microsatellite Instability, Histology, and Survival

Abstract

Lymphocyte-rich gastric carcinomas may have a better prognosis than cancers without a pronounced host inflammatory response. Two subsets of gastric cancer—Epstein-Barr virus-positive and microsatellite instability high—have been associated with a lymphocyte-rich phenotype. We assessed relationships between tumor-infiltrating lymphocytes, Epstein-Barr virus status, microsatellite instability status, and cancer-specific survival in 110 resected gastric cancers. Seven patients had Epstein-Barr virus-positive cancer, including 4 (3.7%) of 107 consecutive patients. Tumors from 17 patients (16%) were designated microsatellite instability high on the basis of negative immunohistochemical staining for MLH1; all tumors had intact expression of MSH2 and MSH6. Epstein-Barr virus-positive cancers had increased tumor-infiltrating lymphocytes compared with Epstein-Barr virus-negative cancers (median 450/10 HPF versus 21/10 HPF, P < .001). Microsatellite instability–high cancers also had increased tumor-infiltrating lymphocytes compared with non–microsatellite instability–high cancers (median 150/10 HPF versus 20/HPF, P < .001). Microsatellite instability–high cancers affected older patients and were more likely to be intestinal in the Lauren classification and expanding in the Ming classification. By univariate analysis, decreased risk of death from gastric cancer was significantly associated with low tumor stage, expanding growth pattern, increasing tumor-infiltrating lymphocyte count, and microsatellite instability–high status. High tumor-infiltrating lymphocyte count and microsatellite instability–high status retained statistical significance as favorable prognostic factors after adjustment for tumor stage in multivariate analysis. Tumor-infiltrating lymphocyte count retained statistical significance as a favorable prognostic factor after adjustment for microsatellite instability–high status; but microsatellite instability–high status did not remain a significant independent prognosticator after adjustment for tumor-infiltrating lymphocyte count. The association between microsatellite instability–high cancers and high tumor-infiltrating lymphocyte counts may account for the association of microsatellite instability–high gastric cancers with improved survival.