PD-L1 expression is an unfavourable prognostic indicator in Asian renal cell carcinomas

J Clin Pathol. 2020 Aug;73(8):463-469. doi: 10.1136/jclinpath-2019-206092. Epub 2020 Jan 24.

Abstract

Background/aims: The programmed cell death receptor 1 (PD-1) checkpoint inhibitor, nivolumab, has been approved for the treatment of metastatic renal cell carcinoma (RCC). However, the understanding of the expression and distribution of PD ligand 1 (PD-L1) in the tumour immune microenvironment and its prognostic role in an Asian cohort is limited. Our group investigated PD-L1 protein expression in a cohort of Asian patients with RCC of mixed ethnicity, using two commercially available antibody clones.

Methods: E1L3N and SP263 anti-PD-L1 clones were used to categorise RCCs of various histological subtypes, diagnosed at our institution between 1995 and 2008, into PD-L1-positive or PD-L1-negative groups, based on a 1% Tumour Proportion Score (TPS) cut-off.

Results: In total, 267 (83%) clear cell (cc)RCC and 55 (17%) non-ccRCC cases were studied. Overall PD-L1 protein expression rates for the entire cohort were 13% and 8% for the E1L3N and SP263 clones, respectively. Patients bearing PD-L1-positive tumours experienced significantly decreased disease-free survival (DFS; E1L3N: p=0.01; SP263: p=0.03) but not overall survival, compared with those with PD-L1-negative tumours. Multivariate survival analysis further confirmed the results of the E1L3N clone (HR 1.85, 95% CI 1.10 to 3.13, p=0.02), but not SP263, after adjusting for pathological stage, histological subtype and grade. The addition of PD-L1 (E1L3N) TPS to clinicopathological features significantly increased the prognostic value for DFS (∆LRχ2=5.25; p=0.022), compared with clinicopathological features alone.

Conclusions: PD-L1 protein expression was associated with an unfavourable prognosis in our study cohort. PD-L1 (E1L3N) expression was an independent prognostic indicator of clinical outcome in all RCCs when using a 1% cut-off.

Keywords: immunopathology; oncology; uropathology.

MeSH terms

  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / mortality*
  • Carcinoma, Renal Cell / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / mortality*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Singapore / epidemiology
  • Tumor Burden
  • Tumor Microenvironment / physiology

Substances

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