Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+ tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT)

Virchows Arch. 2018 May;472(5):815-824. doi: 10.1007/s00428-018-2316-2. Epub 2018 Feb 14.

Abstract

Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor-infiltrating lymphocytes. We analyzed the immunohistochemical (IHC) expression of PD-L1 and PD-1 and their prognostic significance in clinically localized neoplasms in a cohort of 370 ESFT. Slides prepared from tissue microarrays were stained for PD-L1, PD-1, and CD8. Membranous/cytoplasmic staining over 5% of tumor cells was regarded as positive for PD-L1 and PD-1. Prognostic analysis was done considering only clinically localized tumors (n = 217). PD-L1 expression was present in 19% of ESFT, while PD-1 was expressed in 26%. Forty-eight percent of tumors were negative and 12% were positive for both PD-L1 and PD-1. Metastatic tumors displayed higher expression of PD-L1 (p < 0.0001). Histological subtypes were not correlated with PD-L1 or PD-1 positivity. ESFT with elevated proliferation index (Ki-67) were associated with higher PD-L1 expression (p = 0.049). Regarding prognosis, no significant association was found between PD-L1 expression and progression-free survival (PFS) or overall survival (OS), whereas lack of PD-1 expression in tumor cells was correlated with both poor PFS (p = 0.02) and poor OS (p = 0.004). Tumor-infiltrating CD8(+) T lymphocytes were observed in 15.4% of ESFT with informative results (347 tumors). No correlation was found between tumor-infiltrating CD8(+) T lymphocytes and ESFT histological subtypes, tumor location, or PD-1 and PD-L1 expression, nor with PFS (p = 0.473) or OS (p = 0.087). PD-L1 expression was not significantly related to prognosis. PD-1 was expressed in 26% of ESFT tumor cells and may have prognostic and therapeutic implications. CD8 expression in tumor-infiltrating lymphocytes was not related to prognosis.

Keywords: Ewing sarcoma; Immunohistochemistry; PD-1; PD-L1; Prognostic factor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / biosynthesis
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / immunology*
  • Bone Neoplasms / immunology
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / biosynthesis
  • Sarcoma, Ewing / immunology
  • Sarcoma, Ewing / mortality
  • Sarcoma, Ewing / pathology*
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor