The expression of programed death ligand-1 could be related with unfavorable prognosis in salivary duct carcinoma

J Oral Pathol Med. 2018 Aug;47(7):683-690. doi: 10.1111/jop.12722. Epub 2018 May 16.

Abstract

Background: Salivary duct carcinoma (SDC) is a rare tumor occurring in the salivary gland. SDC is a highly aggressive tumor and its prognosis is extremely poor. Effective treatments in advanced SDC have not yet been established. Recently, immune checkpoint inhibitors have paved the way for the treatment of various malignancies. We examined the expressions of programed death ligand (PD-L) 1/PD-L2 and programed death (PD-1), and the correlation of clinicopathological findings.

Methods: We examined 18 cases of SDC and conducted immunohistochemical staining using formalin-fixed paraffin-embedded full-face sections.

Results: The expression of PD-L1 and PD-L2 in tumor cells was observed in nine cases (50%) and 14 cases (78%), respectively. Cases with a high expression of PD-L1 and PD-L2 were found in four (22%) and seven cases (39%), respectively. The cases with a high expression of PD-L1 showed significantly shorter overall survival compared to those with low PD-L1 expression and null expression. We also examined the expression of PD-L1/PD-L2 and PD-1 of tumor-infiltrating mononuclear cells (TIMC) in stroma. The expressions of PD-L1 in tumor cells and stroma had a significant correlation. Association between the expressions of PD-L1 in tumor cells and those of PD-1 in stroma was significant. However, PD-L2 expression in the tumor had no significant correlation with expression in TIMCs. PD-L1, PD-L2 and PD-1 expressions in stroma were not associated with patient prognosis.

Conclusions: High PD-L1 expression in SDC was strongly associated with unfavorable prognosis, indicating that PD-1/PD-L1 inhibitors could be effective in SDC.

Keywords: PD-1; PD-L1; PD-L2; immunohistochemical staining; salivary duct carcinoma.

MeSH terms

  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism*
  • Female
  • Gene Expression*
  • Genetic Association Studies*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein / genetics
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Programmed Cell Death 1 Receptor / genetics*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Salivary Ducts*
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / mortality
  • Survival Rate

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor