37P - Association of PDL1 expression with TP53, KRAS mutation, and microsatellite instability in Indonesian patients with colorectal cancer (37P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Cancer Immunology and Immunotherapy
Translational Research
Presenter Teguh Putra
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors T.P. Putra1, G.D. Kusumo1, A. Budiyati1, F. Rexana2, A. Sudoyo3, A.N. Kurniawan2, A.R. Utomo4, A. Utama1
  • 1Cancer, Stem Cell and Cancer Institute (SCI), PT Kalbe Farma Tbk, 13210 - Jakarta/ID
  • 2Oncology, Medistra Hospital, 12950 - Jakarta/ID
  • 3Oncology Hematology, Universitas Indonesia, 12950 - Jakarta/ID
  • 4Cancer, Kalbe Genomic, 13210 - Jakarta/ID

Abstract

Background

Immune checkpoint blocking therapies have yielded positive clinical data in a series of human malignancies, including microsatellite instability in colorectal carcinoma (CRC). Programmed cell death 1 (PD1) and its ligand (PDL1) are key suppressors of the cytotoxic immune response. Previous study found that PDL1 expression was regulated by p53 gene. This study aims to investigate association of PDL1 expressions with TP53, KRAS mutations and microsatellite instability (MSI) in colorectal cancer patients.

Methods

Sixty one samples from CRC patients were immunohistochemically stained using antibodies to detect PDL1 and P53 expressions. Moreover, antibodies against mismatch repair or MMR (MLH1, MSH2, PMS2, and MSH6) proteins were used to assess MSI. The same samples were also tested for KRAS mutations in exons 2 (codon 12 and 13) using PCR high resolution melt (HRM) and direct DNA sequencing. The study was approved by Ethics Committee of Medistra Hospital.

Results

High tumor PDL1 expressions were found in 25% (15/61) patients. Meanwhile MSI was detected in 9 out of 61 patients (15%). Most MSI patients (7 of 9) had positive PDL1 expressions. In contrary only 8 out of 52 MSI negative patients showed PDL1 expressions suggesting significant association of PDL1 expressions with MSI status (p = 0,0004). PDL1 expressions tend to be higher in P53 wildtype (38%) than P53 mutant (18%, p = 0.17). Similarly PDL1 expression tend to be higher in KRAS wildtype (30%) than KRAS Mutant (11%, p = 0.19).

Conclusions

PDL1 expression is strongly associated with MSI in Indonesian CRC patients. MSI screening may be useful to predict patients with high PDL1 expressions and eligibility to anti PD1 immunecheckpoint therapy.

Clinical trial identification

Legal entity responsible for the study

PT Kalbe Farma Tbk.

Funding

PT Kalbe Farma Tbk, Stem Cell and Cancer Institute (SCI)

Disclosure

All authors have declared no conflicts of interest.