PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer

Hum Pathol. 2016 Sep:55:182-9. doi: 10.1016/j.humpath.2016.05.012. Epub 2016 May 31.

Abstract

The mechanism of carcinogenesis of gastric cancer (GC) is still unclear now. This study aimed to explore the correlations among PD-L1, Epstein-Barr virus (EBV) infection, lymphocyte infiltration, HER2 expression, HER2 gene status, histology, and other clinicopathological factors in GC. A total of 44 GC patients with massive lymphocyte infiltration (GC-MLI) and 93 GC patients without massive lymphocyte infiltration were involved in this study. Immunohistochemical analysis was used to test the expression levels of PD-L1 and HER2. Fluorescence in situ hybridization was used on HER2-positive cases with a score of 2+ to test the HER2 gene status. EBV-encoded RNA was used to test for EBV infection. In univariate analysis, PD-L1 expression was significantly associated with GC-MLI (P<.001), lower age (P=.019), EBV infection (P<.001), lower HER2 expression (P=.011), and diffuse/mixed type of histology (P=.022). EBV-encoded RNA-positive cases were significantly associated with GC-MLI (P<.001), lower age (P=.016), diffuse/mixed type of histology (P=.011), and lower HER2 expression (P=.032). In the multivariate logistic regression model, GC-MLI and the diffuse/mixed type histology were identified as 2 independent factors that affected PD-L1 expression (P<.001). Furthermore, PD-L1-positive cases have worse overall survival than do PD-L1-negative cases (P=.011). These results suggest that massive lymphocyte infiltration and the diffuse/mixed type histology of GC should be taken into consideration to select the appropriate patients for PD-L1 inhibitory treatment in the future.

Keywords: EBV; Gastric cancer; HER2; PD-L1; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / analysis*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Chi-Square Distribution
  • Female
  • Herpesvirus 4, Human / genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lymphocytes, Tumor-Infiltrating / virology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • RNA, Viral / genetics
  • Receptor, ErbB-2 / genetics
  • Retrospective Studies
  • Risk Factors
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / virology

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • RNA, Viral
  • ERBB2 protein, human
  • Receptor, ErbB-2