The Clinical Significance of PD-L1/PD-1 Expression in Gastroenteropancreatic Neuroendocrine Neoplasia

Ann Clin Lab Sci. 2019 Sep;49(4):448-456.

Abstract

Purpose: This study examined the tumor expression of programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) in patients with GEP-NEN. This study aims to reveal the relationship of their expression with clinicopathological characteristics and prognosis.

Methods: PD1 and PD-L1 expression in tumors from 120 GEP-MEN patients was evaluated using immunohistochemistry. The correlations of the expression of PDL1/PD1 and clinicopathological features were assessed.

Results: Immunohistochemical staining indicated that PD-L1 was expressed in the tumor cells of 52.5% patients with GEP-NENs, and PD-L1 expression was positively correlated with the World Health Organization (WHO) classification, American Joint Committee on Cancer (AJCC) stage, lymphatic metastasis and prognosis. Meanwhile, PD-1 was expressed in tumor infiltrating lymphocytes within 55.8% tumor samples, and PD-1 expression was positively correlated with AJCC stage and GEP-NENs prognosis. Moreover, survival analysis indicated that the overall median survival of patients with PD-L1/PD-1-positive tumors significantly differed from that of patients with PD-L1/PD-1-negative tumors. Multivariate analysis confirmed that AJCC stage and Chromogranin A expression in tumor tissues were independent prognostic factors for overall survival. In conclusion, PDL1 was an independent prognostic factor for patients with GEP-NENs. Our results suggested that patients with GEP-NENs might be appropriate for PD1/PDL1-targeted therapy.

Conclusions: Our findings show that the expression of PD-L1 and PD-1 correlates with patient prognosis, and may thus serve as potential pathological prognostic markers of GEP-NENs. Immunotherapy using PD-1/PD-L1 inhibitors may be a promising strategy for GEP-NENs patients with PD-L1/PD-1 positively expressed.

Keywords: PD-1; PD-L1; gastroenteropancreatic neuroendocrine neoplasia; immunohistochemistry; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Child
  • Female
  • Humans
  • Intestinal Neoplasms / metabolism*
  • Intestinal Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Programmed Cell Death 1 Receptor

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor