The impact of programmed cell death-ligand 1 (PD-L1) and CD8 expression in grade 3 endometrial carcinomas

Int J Clin Oncol. 2019 Nov;24(11):1419-1428. doi: 10.1007/s10147-019-01484-0. Epub 2019 Jun 13.

Abstract

Background: To evaluate the expression of programmed cell death-ligand 1 (PD-L1) and CD8 in high-grade endometrial carcinomas and relate it to several clinicopathological parameters.

Methods: One hundred and one (101) patients with high-grade endometrial carcinomas who were completely surgically staged were included in this study. PD-L1 and CD8 + expression was evaluated by immunohistochemistry.

Results: In our cohort, 47 women (46.5%) had endometrioid carcinomas and 54 patients (53.5%) were diagnosed with non-endometrioid cancers. In endometrioid carcinomas, there was a significantly higher rate of positivity for PD-L1 expression (p = 0.042) and of intraepithelial CD8 + cell counts (p = 0.004) as opposed to non-endometrioid cancers. There were no significant relationships with any of the other clinicopathological features under study. Univariate and multivariate analysis revealed that only high intraepithelial CD8 + counts (p = 0.01) was associated with longer progression-free survival. Tumors positive for PD-L1 and high intraepithelial CD8 expression were mainly of endometrioid histology, whilst PD-L1-positive/CD8 low and PD-L1-negative/CD8 low tumors were mostly non-endometrioid carcinomas (p = 0.01). PD-L1 negative/CD8 high tumors had the longest progression-free survival (p = 0.032).

Conclusions: In grade 3 endometrial carcinomas, both of endometrioid and non-endometrioid type, high intraepithelial CD8 + counts represent an independent favorable prognostic factor and when related to PD-L1-negative tumors, a longer progression-free survival can be predicted. Immunotherapy could probably be considered for PD-L1-positive/CD8 + high tumors, which were mostly of endometrioid histology.

Keywords: CD8; Endometrial cancer; PD-L1.

MeSH terms

  • Aged
  • Apoptosis
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / mortality
  • Carcinoma, Endometrioid / pathology*
  • Carcinoma, Endometrioid / therapy
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology*
  • Endometrial Neoplasms / therapy
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Prognosis
  • Survival Analysis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CD8 Antigens