Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva

J Cancer Res Clin Oncol. 2019 Jun;145(6):1651-1660. doi: 10.1007/s00432-019-02915-1. Epub 2019 Apr 10.

Abstract

Purpose: Squamous cell carcinoma of the vulva (SQCV) is the fifth most common cancer in women and accounts for about 5% of all genital cancers in women. The PD-L1 signaling pathway is activated in many malignant neoplasms and its blockade enhances anti-cancer immunity. The aim of our study was to examine the protein expression of PD-L1 and PD-1 in squamous cell cancer of the vulva, its correlations with clinicopathologic features and prognostic value.

Methods: Patients with SQCV treated in one institution were used for the analyses. PD-L1 immunohistochemistry was performed on 4 µm-thick section of the respective FFPE tissue blocks using the 28-8 antibody. PD-L1 scoring was performed separately for tumour cells (TC) and tumour associated immune cells. DNA was extracted to determine HPV status. Kaplan-Meier estimates for disease-free-survival and overall-survival were calculated and compared by log-rank test.

Results: PD-L1 expression in tumour cells could be observed in 32.9% of the patients. The expression of PD-L1 in peritumoural immune cells was confirmed in 91.4% of the patients. A significant correlation between PD-L1 expression in tumour cells and tumour stage was detected (p = 0.007). PD-L1 expression was independent from HPV status. Using the log-rank test we could not prove any significant differences in disease-free survival (p = 0.434) and overall survival (p = 0.858). Regression analysis showed that nodal status is a predictive factor of survival (p < 0.001).

Conclusion: The present study showed that a relevant amount of patients with squamous cell cancer of the vulva express PD-L1 in both, tumour cells and tumour-associated immune cells. Furthermore, the significant correlation of PD-L1 expression in TCs with tumour stage indicated the clinical impact of PD-L1 expression during tumour development. These data indicate that SQCV might be amenable to immune checkpoint-inhibition and constitute a rational for the future clinical trials.

Keywords: HPV; PD-1; PD-L1; Vulvar carcinoma.

MeSH terms

  • Aged
  • B7-H1 Antigen / biosynthesis
  • B7-H1 Antigen / immunology
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / immunology
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Programmed Cell Death 1 Receptor / biosynthesis*
  • Programmed Cell Death 1 Receptor / immunology
  • Vulvar Neoplasms / immunology
  • Vulvar Neoplasms / metabolism*
  • Vulvar Neoplasms / pathology

Substances

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