title: PD-L1 Expression in Clear Cell Renal Cell Carcinoma: An Analysis of Nephrectomy and Sites of Metastases.
abstract: BACKGROUND
  Expression of programmed death ligand (PD-L1/B7-H1/CD274) represents a mechanism of immune escape for renal cell carcinoma (RCC) cells. Drugs blocking PD-L1 or its receptor are in clinical development and early data suggests that tumor PD-L1 expression may predict response.
  
  
  METHODS
  A tissue microarray (TMA) consisting of four biopsy cores from 34 matched pairs of nephrectomy and metastatic sites of clear cell RCC was used to assess PD-L1 expression by quantitative immunofluorescence. Assessment of intra- and inter-tumor heterogeneity and primary and metastatic tumor expression was performed using a method of Automated Quantitative Analysis (AQUA).
  
  
  RESULTS
  The median AQUA scores were higher in metastatic than primary specimens (P < 0.0001). The correlation between PD-L1 expression in matched primary and metastatic specimens was weak (R= 0.24). Within a given tumor, variable PD-L1 staining heterogeneity was seen, however the degree of heterogeneity was similar in primary and metastatic sites (P = 0.482).
  
  
  CONCLUSIONS
  The weak correlation between PD-L1 expression in primary and metastatic sites for a given patient suggests that expression in nephrectomy specimens cannot be used to select metastatic RCC patients for PD-L1 and PD-1 inhibitors. The intra-tumor heterogeneity seen in both primary and metastatic specimens indicates that a single core biopsy might not be sufficient to determine PD-L1 expression.
authors.affiliation: 1. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Jilaveanu
authors.affiliation: 2. Department of Urology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: B
authors.initials: B
authors.lastname: Shuch
authors.affiliation: 1. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA ; 3. Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, CT, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Zito
authors.affiliation: 4. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: F
authors.initials: F
authors.lastname: Parisi
authors.affiliation: 1. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Barr
authors.affiliation: 4. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kluger
authors.affiliation: 5. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: 1. Departments of Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Kluger
keywords: PD-L1; renal cell carcinoma