In papillary thyroid carcinoma, expression by immunohistochemistry of BRAF V600E, PD-L1, and PD-1 is closely related

Virchows Arch. 2018 May;472(5):779-787. doi: 10.1007/s00428-018-2357-6. Epub 2018 Apr 12.

Abstract

Immune checkpoint inhibitor therapies targeting PD-L1/PD-1 have been shown to be effective in treating several types of human cancer. In papillary thyroid carcinoma (PTC), little is known about the expression of PD-L1/PD-1 in the tumor microenvironment or its potential correlation with BRAF V600E mutation status. In this study, we examined the expression of PD-L1, PD-1, and BRAF V600E in PTC by immunohistochemistry and investigated the clinical significance of expression status. We studied the expression of PD-L1, PD-1, and BRAF V600E by immunohistochemical staining in 110 cases of PTC with a diameter > 1 cm. Cases with a background of chronic lymphocytic thyroiditis (CLT) were excluded, as differentiating lymphocytes in the context of CLT from tumor-infiltrating lymphocytes (TILs) is difficult. We classified PD-L1+/PD-1+ expression as type 1 (41%), PD-L1-/PD-1- as type 2 (17%), PD-L1+/PD-1- as type 3 (5%), and PD-L1-/PD-1+ as type 4 (37%). Significant correlations were found between expression of BRAF V600E and that of PD-L1 and PD-1. The positive correlation observed between expression of BRAF V600E and PD-L1/PD-1 suggests that immunotherapies targeting PD-L1/PD-1 might be effective for PTC patients with the BRAF V600E mutation, which are refractory to radioiodine therapy.

Keywords: BRAF V600E; Immunohistochemistry; PD-1; PD-L1; Papillary thyroid carcinoma.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Papillary / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / analysis
  • Programmed Cell Death 1 Receptor / biosynthesis*
  • Proto-Oncogene Proteins B-raf / analysis
  • Proto-Oncogene Proteins B-raf / biosynthesis*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / metabolism*

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf