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

Heidi D. Lehrke, Rondell Graham, Robert R Mc Williams, Dora M. Lam-Himlin, Thomas Christopher Smyrk, Sarah Jenkins, Haidong M Dong, Lizhi Zhang

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)441-449
Number of pages9
JournalAmerican Journal of Clinical Pathology
Volume148
Issue number5
DOIs
StatePublished - Nov 2 2017

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Ligands
Carcinoma
Neoplasms
Adenocarcinoma
Pancreatic Carcinoma
DNA Mismatch Repair
B-Lymphocytes
Clone Cells
Immunohistochemistry
Macrophages
T-Lymphocytes
Therapeutics
Proteins

Keywords

  • Immunohistochemistry
  • Pancreatic ductal adenocarcinoma
  • PD-L1
  • Undifferentiated pancreatic carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and Extent of PD-L1 Expression by Tumor Cells. / Lehrke, Heidi D.; Graham, Rondell; Mc Williams, Robert R; Lam-Himlin, Dora M.; Smyrk, Thomas Christopher; Jenkins, Sarah; Dong, Haidong M; Zhang, Lizhi.

In: American Journal of Clinical Pathology, Vol. 148, No. 5, 02.11.2017, p. 441-449.

Research output: Contribution to journalArticle

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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.",
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AU - Lehrke, Heidi D.

AU - Graham, Rondell

AU - Mc Williams, Robert R

AU - Lam-Himlin, Dora M.

AU - Smyrk, Thomas Christopher

AU - Jenkins, Sarah

AU - Dong, Haidong M

AU - Zhang, Lizhi

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N2 - 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.

AB - 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.

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