PD-L1 Expression Correlates With Young Age and CD8+ TIL Density in Poorly Differentiated Cervical Squamous Cell Carcinoma

Int J Gynecol Pathol. 2020 Sep;39(5):428-435. doi: 10.1097/PGP.0000000000000623.

Abstract

Management options are limited in advanced or recurrent cervical carcinoma. The Food and Drug Administration has recently approved programed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) inhibitors for the treatment of advanced PD-L1 positive cervical cancer. We studied PD-L1 expression in cervical squamous cell carcinoma (CSCC) samples initially on a The tissue microarray and then in full-tissue sections from poorly differentiated (grade 3) cancers. Tissue microarray was composed of 45 grade 3 and 2 (moderately differentiated) tumors. PD-L1 expression was evaluated as categorical data and by obtaining combined positive score of neoplastic and mononuclear inflammatory cells. In tissue microarray samples PD-L1 expression was higher in poorly differentiated cancers compared with grade 2 tumors by immunohistochemistry. Full-tissue sections from grade 3 CSCC (n=22) were stained with PD-L1, CD8, and VEGF antibodies. Poorly differentiated CSCC samples had diffuse (≥50%) and focal/patchy staining patterns. The latter pattern showed localized tumor-stroma interface staining in 5 samples with low combined positive score. Importantly, younger patients (median=36) had tumors with higher expression. PD-L1 expression was associated with larger tumor size and absent lymphovascular invasion. In addition, CD8 tumor-infiltrating lymphocyte density within the neoplastic tissue matched with PD-L1 levels. The overall survival rates did not correlate with PD-L1 expression. However, in early-stage disease high CD8 tumor-infiltrating lymphocyte density within the peritumoral stroma was associated with better survival outcomes in multivariate analysis. PD-L1 expression and CD8 tumor-infiltrating lymphocyte density may be useful to define a subgroup of patients with relatively better prognosis in poorly differentiated CSCC. It is warranted to validate our results in a larger sample size.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / pathology*
  • Cell Differentiation
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Prognosis
  • Survival Rate
  • Tissue Array Analysis
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CD8 Antigens
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A