Frequency of mismatch repair protein deficiency and PD-L1 in high-grade gliomas in adolescents and young adults (AYA)

Brain Tumor Pathol. 2021 Jan;38(1):14-22. doi: 10.1007/s10014-020-00379-7. Epub 2020 Sep 8.

Abstract

Central nervous system tumors in adolescents and young adults (AYA) are rarely reported in the literature. The association with cancer predisposition syndrome is not established. Programmed death ligand 1 (PD-L1) can predict the potential response of patients to immunotherapy. A link between mismatch repair protein deficiency (MMRP-D) and response to immunotherapy is established. P53 is reported to be positive in MMRD-D cases. We aim to investigate the frequency of MMRP-D in AYA with high-grade glioma and any potential association with PD-L1. A total of 96 cases were tested including 49 (51.0%) cases of glioblastoma. Six cases (6.25%) were MMRP-D, 17 (17.7%) were PD-L1 positive, mostly in grade IV tumors (8.7% in grade III compared to 26% in grade IV, p value = 0.027), and 69 (71.9%) were P3 positive. None of the MMRP-D cases expressed PD-L1. P53-positive cases were mostly MMRP proficient (n = 67; 74.4%, p value 0.051). Fourteen cases (28.7%) were positive for both PD-L1 and P53, while p53-positive grade IV tumors were mostly associated with negative PD-L1 (n = 29, 58%, p value = 0.043). MMRP deficiency does not appear to be prevalent in high-grade glioma in AYA. Expression of PD-L1 in a quarter of cases might suggest a role for immunotherapy in high-grade glioma.

Keywords: Adolescents and young adults; Central nervous system tumors; Glioblastoma; High-grade glioma; Mismatch repair protein; Mismatch repair protein deficiency; PD-L1.

MeSH terms

  • Adolescent
  • Adult
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Colorectal Neoplasms / genetics*
  • DNA Mismatch Repair / genetics*
  • Female
  • Gene Expression
  • Glioma / genetics*
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Immunotherapy
  • Male
  • Neoplasm Staging
  • Neoplastic Syndromes, Hereditary / genetics*
  • Retrospective Studies
  • Tumor Suppressor Protein p53
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Turcot syndrome