Expression of programmed death-1 in sentinel lymph nodes of breast cancer

J Surg Oncol. 2018 May;117(6):1131-1136. doi: 10.1002/jso.24937. Epub 2017 Nov 28.

Abstract

Background and objectives: To explore whether lymphocytes in sentinel lymph nodes (SLNs) are highly exposed to tumor neoantigens and thus express high level of programmed death 1 (PD-1), we examined PD-1 expression in SLNs and non-sentinel regional lymph nodes (non-SLNs) in breast cancer.

Methods: We performed PD-1 immunohistochemistry in two cohorts: 40 metastasis-negative SLNs including 10 patients for each subtype (luminal A-like, luminal B-like, HER2, and triple negative breast cancer [TNBC]); and 25 pairs of metastasis-positive SLNs and non-SLNs (10 luminal A-like, 10 luminal B-like, and 5 TNBC).

Results: Among 40 metastasis-negative SLNs, 34 and 6 samples were PD-1 intensity grade 1 (low) and 2 (high), respectively. PD-1 intensity correlated with PD-1-positive lymphocyte numbers (P = 0.005); TNBC had the highest PD-1 lymphocyte numbers among all subtypes. The median PD-1-positive lymphocyte number was higher in SLNs than non-SLNs. In most cases, more lymphocytes in SLNs expressed PD-1 than those in non-SLNs (P < 0.0001).

Conclusions: TNBC had the greatest PD-1 expression among all subtypes, and metastasis-positive SLNs had more PD-1-positive lymphocytes than downstream non-SLNs. These data suggested that lymphocytes in SLNs are activated following exposure to tumor neoantigens and thus tumor specific, and could be utilized as a biomarker platform.

Keywords: PD-1; breast cancer; sentinel lymph node.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*
  • Sentinel Lymph Node / metabolism
  • Sentinel Lymph Node / pathology*
  • Sentinel Lymph Node / surgery
  • Sentinel Lymph Node Biopsy
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*
  • Triple Negative Breast Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor