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Standards of diagnosis and treatment of brain tumours

2051 - Mismatch Repair deficiency (MMRD) and PD-L1 expression in High Grade Glioma (HGG) patients from Siloam Hospital Jakarta Indonesia (119O)

Date

18 Nov 2017

Session

Standards of diagnosis and treatment of brain tumours

Topics

Translational Research;  Central Nervous System Malignancies

Presenters

Diana Patricia

Citation

Annals of Oncology (2017) 28 (suppl_10): x35-x38. 10.1093/annonc/mdx657

Authors

D. Patricia1, J. July2, E.J. Wahjoepramono2, G. Prayogi3, Z.G. Wuisan4, D. Budhiarko3, T.P. Putra3, N. Masykura3, A.R. Utomo5

Author affiliations

  • 1 Faculty Of Medicine Department Of Anatomic Pathology, Universitas Pelita Harapan, 15810 - Tangerang/ID
  • 2 Faculty Of Medicine Department Of Anatomic Neurosurgery, Universitas Pelita Harapan, 15810 - Tangerang/ID
  • 3 Cancer Diagnostics, Stem-cell and Cancer Institute, PT Kalbe Farma Tbk, 13210 - Jakarta/ID
  • 4 Institute Of Pharmaceutical Biology, Rheinische Friedrich-Wilhelms-University, D-53113 - Bonn/DE
  • 5 Cancer Diagnostics, Stem-cell and Cancer Institute & Kalbe Genomics Laboratory, PT Kalbe Farma Tbk, 13210 - Jakarta/ID
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Abstract 2051

Background

High Grade Glioma (HGG) is the most common adult CNS tumor and known by its high tumor mutation load (TML). Mismatch repair protein (MMR) is a set of proteins (namely MLH1 and MSH2) that are responsible to maintain genomic integrity. Loss of MMR expressions or Mismatch Repair Deficiency (MMRD) may lead to TML inducing production of neoantigens and iliciting cellular immune responses. Programmed death-ligand 1 (PD-L1) is widely known as co-inhibitory ligand which is responsible for immune evasion by tumor cells. The interaction among MMRD, PD-L1 and apoptotic factor, TP53, in HGG has been subjects of our investigation within patient cohort treated in Indonesian private hospital.

Methods

We performed Immunohistochemistry (IHC) assays on 43 High Grade Glioma FFPE samples from Siloam Hospital. The assay were optimized to detect MLH1, MSH2, TP53 and PD-L1 protein expression. E1L3N antibody was used to detect PD-L1 expression. MMR deficient was defined as loss of at least one of MMR proteins (MLH1, MSH) expressions. Statistical analysis were used to describe association among biomarkers as well as the age group and histological classification [Glioblastoma Multiforme (GBM) vs Other HGG (Non-GBM)].

Results

Four sample which not qualified were omitted from analysis. MMRD were found in 33% patient (13/39) and was associated with negative expression of TP53 (p = 0.0161), suggesting TP53 independent pathway of genetic instability. PD-L1 positive rate tend to be higher in MMRD (38%) than MMR proficient (MMRP 11%) cohorts, albeit not statistically significant (p = 0.0896). There is no significant relationship between MMRD and age group as well as histological status. Overall survival analyses showed MMRD was associated with poor prognosis (p = 0.005).

Conclusions

MMRD may serve as useful prognostic biomarker predicting patients with poor survival. Moreover, a subset of patients with MMRD may express PD-L1 protein, a prominent predictive biomarker for immune checkpoint therapy.

Clinical trial identification

Legal entity responsible for the study

Universitas Pelita Harapan Faculty of Medicine

Funding

Kalbe Farma Tbk

Disclosure

All authors have declared no conflicts of interest.

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