Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and Extent of PD-L1 Expression by Tumor Cells

Am J Clin Pathol. 2017 Nov 2;148(5):441-449. doi: 10.1093/ajcp/aqx092.

Abstract

Objectives: Programmed death ligand 1 (PD-L1) expression in pancreatic ductal adenocarcinoma (PDA) has been described, but unselected PDAs have shown limited clinical responsiveness to anti-programmed death 1 (PD-1)/PD-L1 therapy.

Methods: We studied 24 cases of undifferentiated pancreatic carcinoma (UPC) using immunohistochemistry for PD-L1 (E1L3N clone), CD3, CD20, CD68, and DNA mismatch repair proteins in this study. Slides were scored for extent of PD-L1 expression on tumor cells and tumor-infiltrating immune cells.

Results: PD-L1 expression was more frequent in UPCs than in PDAs (63% vs 15%, P < .01). The extent of PD-L1 expression was greater in UPCs, with 13 (87%) of 15 cases containing 10% or more positive tumor cells compared with three of seven PDAs (P = .05). Both tumor groups showed similar numbers of tumor-infiltrating T cells, B cells, and macrophages.

Conclusions: UPC is enriched for PD-L1 expression in frequency and extent, relative to conventional PDA. Anti-PD-1/PD-L1 agents may represent a valuable therapeutic approach for this subset of highly aggressive pancreatic carcinoma.

Keywords: Immunohistochemistry; PD-L1; Pancreatic ductal adenocarcinoma; Undifferentiated pancreatic carcinoma.

Publication types

  • Historical Article

MeSH terms

  • Aged
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Female
  • History, 16th Century
  • History, 17th Century
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Proportional Hazards Models

Substances

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