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124P - Detection of KRAS mutation, MSI and TP53 status in Indonesian CRC patients with its association to PD-L1 expression

Presentation Number
124P
Lecture Time
17:10 - 17:10
Speakers
  • Gita D. Kusumo (east jakarta, ID)
Session Name
Location
Foyer La Scene, Paris Marriott Rive Gauche, Paris, France
Date
05.03.2018
Time
17:10 - 18:00
Authors
  • Gita D. Kusumo (east jakarta, ID)
  • Teguh P. Putra (east jakarta, ID)
  • Akterono D. Budiyati (east jakarta, ID)
  • Fritzie Rexana (Jakarta, ID)
  • Aru Sudoyo (Jakarta, ID)
  • Antonius N. Kurniawan (Jakarta, ID)
  • Ahmad R. Utomo (east jakarta, ID)
  • Andi Utama (east jakarta, ID)

Abstract

Background

KRAS and microsatellite instability (MSI) status are well established markers in personalized therapy of colorectal cancer (CRC). The immune checkpoint inhibitor Programmed Death 1 (PD1) and its ligand (PD-L1) have been reported in recent studies as promising targets for cancer therapy. However, there is still a debatable result in the correlation between PD1/PD-L1 expression and KRAS and MSI status as the essential CRC biomarker. Therefore, this study aims to characterize molecular profiles of KRAS, MSI, and TP53 in their association with PD-L1 expression in an Indonesian CRC patient cohort.

Methods

We screened formalin-fixed paraffin-embedded (FFPE) samples from 88 CRC patients for three biomarkers (KRAS, TP53 and PD-L1) and their MSI status. MSI status was defined by the MMR protein expression (MSH2, MLH1, PMS2, MSH6) using monoclonal antibodies by immunohistochemistry (IHC) methods. IHC was also used to detect PD-L1 and TP53 protein expression. High resolution melting PCR along with Sanger sequencing were carried out to detect KRAS mutation status. All the data was statistically analyzed using Fischer exact test.

Results

Only 12.6% (16 out of 88) of sample showed PD-L1 expression. Statistical analysis showed the association between MSI with PD-L1 expression (p = 0.0001). The study showed no association between PD-L1 expression with TP53 (p = 0.9164) and KRAS status (p = 0.3749). Despite that, PD-L1 expression still tended to be higher in patients with wild type KRAS (82.3%/17.7%; wt/mut) and TP53 (62.5%/37.5%; wt/mut).

Conclusions

PD-L1 expression was associated with patient MSI status in this Indonesian cohort. Defining a patient’s MSI status could be suggested as an important step in a screening process for CRC treatment while using anti PD1/PD-L1 targeted therapy.

Legal entity responsible for the study

Institutional Review Board, Stem Cell and Cancer Institute, Jakarta

Funding

PT. Kalbe Farma Tbk., Jakarta, Indonesia

Disclosure

All authors have declared no conflicts of interest.

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