Prognostic implication of programmed cell death 1 protein and its ligand expressions in endometrial cancer

Gynecol Oncol. 2018 May;149(2):381-387. doi: 10.1016/j.ygyno.2018.02.013. Epub 2018 Mar 21.

Abstract

Objective: Monoclonal antibodies targeting programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) demonstrated promising clinical response. The predictive/prognostic value of PD-1/PD-L1 immunohistochemistry (IHC) has been evaluated in many cancer types. However, the prognostic value of PD-1/PD-L1 IHC has not been evaluated in endometrial cancer.

Methods: We conducted a retrospective study to quantify the IHC CD8, PD-1, and PD-L1 expressions in immune cells at center of tumor (CT), invasive margin (IM), and/or tumor cell in 183 primary endometrial cancer samples from a single cohort, followed by their reciprocal combinations, including compartmental differences, and correlated them with overall survival (OS) and progression-free survival (PFS).

Results: In repeated Cox multivariable models adjusted by clinicoimmunopathologic factors, high CT-PD-L1 was an independent adverse prognostic factor for PFS in all patients and in the microsatellite-stable subgroup. Immune marker ratios revealed independently shorter PFS for high CT-PD-L1/CT-CD8 and CT-PD-L1/CT-PD-1 ratios. Classification of endometrial cancer into four groups based on CT-CD8 and CT-PD-L1 revealed significantly different survival among groups.

Conclusions: The high PD-L1/CD8 ratio and the high expression of PD-L1 on immune cells were independent poor prognostic factors for PFS in endometrial cancer, providing insights into the tumor microenvironment.

Keywords: Endometrial cancer; Immunohistochemistry; Prognostic factor; Programmed cell death 1 ligand 1; Tumor microenvironments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / immunology
  • Carcinoma, Endometrioid / immunology*
  • Endometrial Neoplasms / immunology*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / biosynthesis*
  • Programmed Cell Death 1 Receptor / immunology
  • Retrospective Studies

Substances

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