Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy

Hum Pathol. 2017 Dec:70:49-54. doi: 10.1016/j.humpath.2017.10.003. Epub 2017 Oct 14.

Abstract

Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease.

Keywords: Digestive system; Immunotherapy; Neuroendocrine carcinoma; PD-1; PD-L1.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / analysis*
  • B7-H1 Antigen / antagonists & inhibitors
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / antagonists & inhibitors
  • Carcinoma, Neuroendocrine / chemistry*
  • Carcinoma, Neuroendocrine / drug therapy
  • Carcinoma, Neuroendocrine / pathology
  • Cell Differentiation*
  • Digestive System Neoplasms / chemistry*
  • Digestive System Neoplasms / drug therapy
  • Digestive System Neoplasms / pathology
  • Electronic Health Records
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • New York
  • Predictive Value of Tests
  • Programmed Cell Death 1 Receptor / analysis*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Retrospective Studies
  • Signal Transduction / drug effects
  • Tennessee

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor