Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells in upper tract urothelial carcinoma

Med Oncol. 2017 May;34(5):94. doi: 10.1007/s12032-017-0941-2. Epub 2017 Apr 13.

Abstract

Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway has shown promising results in several malignancies. However, the prognostic significance of PD-L1 expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1 expression and its association with clinicopathological characteristics and oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients with UTUC. Associations of PD-L1 expression on tumor cells and TIMCs with clinicopathological characteristics and cancer-specific survival (CSS) were evaluated. Out of 162 patients, 20 (12.3%) and 35 (21.6%) had positive PD-L1 expression on tumor cells and TIMCs, respectively. Decreased E-cadherin expression was associated with PD-L1 positivity on tumor cells (P = 0.048) and PD-L1 negativity on TIMCs (P = 0.033). PD-L1 expression on tumor cells was higher in patients with preoperative chronic kidney disease (CKD) stage 4-5 than in those with no CKD or CKD stage 1-3 (P = 0.011). PD-L1 was differentially expressed in tumor cells and TIMCs in UTUC. Multivariate analyses revealed that PD-L1 expression on tumor cells independently predicted shorter CSS (P = 0.012), whereas PD-L1 expression on TIMCs independently predicted longer CSS (P = 0.034).

Keywords: Cancer-specific survival; Immunotherapy; Programmed death-ligand 1; Upper tract urothelial carcinoma.

MeSH terms

  • Aged
  • B7-H1 Antigen / biosynthesis*
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / pathology
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Neoplasm Staging
  • Retrospective Studies
  • Ureteral Neoplasms / metabolism*
  • Ureteral Neoplasms / pathology

Substances

  • B7-H1 Antigen
  • CD274 protein, human