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.
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.
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).
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.
Institutional Review Board, Stem Cell and Cancer Institute, Jakarta
PT. Kalbe Farma Tbk., Jakarta, Indonesia
All authors have declared no conflicts of interest.