PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor cells predicts survival in triple-negative breast cancer

Cancer Biol Ther. 2018 May 4;19(5):373-380. doi: 10.1080/15384047.2018.1423919. Epub 2018 Feb 16.

Abstract

To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC) at both protein and mRNA levels, and to analyze the relationship between their expression and clinical parameters of the TNBC patients. Immunohistochemistry and RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte (TILs) abundance was assessed using hematoxylin-eosin staining. Both tumor cells and TILs expressed PDL1. PDL1 protein and mRNA positivity was 6.7% and 74.4% respectively in tumor cells, and 31.3% and 50.9% respectively in TILs. PDL1 protein and mRNA expressions had no significant association with patient prognosis. PD1 protein was only detected in TILs (70.3% positivity). PD1 protein expression was significantly related to PDL1 expression, higher TIL abundance, Ki-67 index, basal-like subtypes, and distant metastasis. Furthermore, it was significantly associated with longer disease free survival (P<0.001) and overall survival (P = 0.004). There was no significant association between PD1 mRNA expression and clinicopathological characteristics. PD1/PDL1 protein and mRNA expressions were inconsistent (kappa = 0.705 and 0.061, respectively). PD1 protein expression in TILs, but not PDL1 in tumor cells, was a favorable prognostic factor in TNBC. PD1/PDL1 mRNA and protein expressions were inconsistent.

Keywords: Immunohistochemistry; RNAscope; basal-like breast cancer (BLBC); programmed cell death ligand 1(PDL1); programmed cell death protein 1(PD1); triple negative breast cancer (TNBC); tumor-infiltrating lymphocytes (TILs).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / immunology
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / biosynthesis*
  • Programmed Cell Death 1 Receptor / immunology
  • Survival Rate
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor