Heterogeneity of PD-L1 expression in primary tumors and paired lymph node metastases of triple negative breast cancer

BMC Cancer. 2018 Jan 2;18(1):4. doi: 10.1186/s12885-017-3916-y.


Background: Programmed cell death ligand 1 (PD-L1) is a potential predictive biomarker of the response to anti-PD-L1/anti- programmed cell death 1 (PD-1) therapy in multiple cancers, including triple negative breast cancer(TNBC). The purpose of this study was to investigate whether PD-L1 expression is homogenous in primary tumors(PTs) and synchronous axillary lymph node metastases(LNMs) of TNBC.

Methods: PD-L1 expression was immunohistochemically evaluated in 101 TNBC patients' PTs and paired LNMs. PD-L1 expression in tumor cells and infiltrating immune cells or node lymphocytes in the PTs and associated LNMs was scored separately and was correlated with patients' clinical parameters and prognoses.

Results: PD-L1 expression exhibited spatial heterogeneity in both the tumor cells and the infiltrating immune cells or node lymphocytes of PTs and LNMs. The PD-L1 expression levels were significantly higher in the lymphocytes and tumor cells of the LNMs than in the PTs. PD-L1 expression was also more frequent among the LNMs. PD-L1 expression was associated with high grade and more stromal tumor-infiltrating lymphocytes(TILs). Furthermore, the disease-free survival and overall survival were similar between the PT- negative/LNM- positive and PT- positive/LNM- positive patients, both of which exhibited worse disease-free survival(DFS) thanPT -negative/LNM -negative patients.

Conclusions: The differential expression of PD-L1 between the PTs and LNMs suggests that LNMs PD-L1 status may be used to indicate whether PD-1/PD-L1-targeted therapy would be suitable for a node-positive TNBC patient in the future.

Keywords: Heterogeneity; Lymph node metastasis; PD-L1; Triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Ductal, Breast / immunology
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Survival Rate
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*


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