Association between programmed cell death ligand-1 expression and extracranial metastasis in intracranial solitary fibrous tumor/hemangiopericytoma

J Neurooncol. 2018 Sep;139(2):251-259. doi: 10.1007/s11060-018-2876-7. Epub 2018 Apr 19.

Abstract

Background: Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) often shows extracranial metastasis, and treatment options are very limited. Immune-checkpoint molecules have not been studied well in SFT/HPCs, and their role in intracranial SFT/HPCs remains unclear.

Methods: We investigated the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and tumor-infiltrating lymphocytes (TIL) in 16 patients of intracranial SFT/HPC by immunohistochemistry to determine if correlation with prognosis exists.

Results: Median overall survival (OS) of 16 patients was 9.2 years, and median follow-up of alive patients was 9.9 years. Recurrence was observed in 13 (81.3%) patients, and extracranial metastasis were observed in 6 (37.5%). PD-L1 expression was observed in all 16 tumors, whereas PD-1 expression was observed in 2. CD3 and CD8 expressions were observed in TILs in 12 and 13 patients respectively. Although the ratio of PD-L1 positive-tumor cells was not associated with OS, progression-free survival, or metastasis-free survival (MFS), diffuse staining of PD-L1 showed a trend toward shorter time to treatment failure (TTF: time to either extracranial metastasis or death) (p = 0.072). Similarly, the intense staining of PD-L1 was associated with shorter MFS (p = 0.0084) and TTF (p = 0.033). CD3 or CD8 expression was not associated with any of the prognostic parameters. In the combined analysis of PD-L1 and CD8, diffuse PD-L1 staining coupled with no or sparse CD8 expression was significantly associated with a shorter TTF (p = 0.005) and showed a trend toward shorter MFS (p = 0.0611).

Conclusions: PD-L1 is frequently expressed in intracranial SFT/HPCs, and diffuse or intense PD-L1 expression might be associated with the early occurrence of extracranial metastases.

Keywords: Extracranial metastasis; PD-1; PD-L1; SFT/HPC; Tumor infiltrating lymphocyte.

MeSH terms

  • Adolescent
  • Adult
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Hemangiopericytoma / metabolism*
  • Hemangiopericytoma / mortality
  • Hemangiopericytoma / pathology
  • Hemangiopericytoma / therapy
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis / diagnosis*
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*
  • Solitary Fibrous Tumors / metabolism*
  • Solitary Fibrous Tumors / mortality
  • Solitary Fibrous Tumors / pathology
  • Solitary Fibrous Tumors / therapy
  • Survival Analysis
  • Treatment Failure
  • Young Adult

Substances

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