Evaluation of MMR Status and PD-L1 Expression Using Specimens Obtained by EUS-FNB in Patients with Pancreatic Ductal Adenocarcinoma (PDAC)

Abstract

Deficient DNA mismatch repair status (dMMR)/high microsatellite instability have been shown to be predictive biomarkers for immune checkpoint inhibitor drugs which block the programmed death protein-1/programmed death ligand-1 (PD-1/PD-L1) interaction between tumor cells and activated T cells. The aim of this study was to determine the prevalence of MMR status and quantification of PD-L1 expression in pancreatic endoscopic ultrasound-guided fine-needle biopsy (EUS FNB) specimens. Immunochemistry (IHC) was performed on consecutive archived treatmentnaïve formalin-fixed paraffin-embedded EUS-FNB samples. The specimens were considered to have PD-L1 expression if PD-L1 was expressed in ≥1% of tumor cells and a high level of expression if ≥50%. Tumors with absent nuclear staining of DNA mismatch repair proteins (MLH1, MSH2, MSH6, or PMS2) were classified as dMMR. A total of 28 treatment-naïve patients who underwent EUS-FNB and had a final diagnosis of pancreatic ductal adenocarcinoma (PDAC) were included in the study. All the EUS-FNB samples were adequate for the evaluation of MMR and PD-L1 expression. None of the patients with PDAC included in the study had a dMMR tumor. PD-L1 expression was identified in 39% of the cohort (n = 11). Expression thresholds of ≥1%, ≥10%, and ≥50% in tumor cells were identified in 11 (39%), 4 (14%), and 1 (4%) patients, respectively. The evaluation of MMR status and PD-L1 can be successfully performed on EUS-FNB pancreatic specimens. Furthermore, MMR expression failed to show utility in recognizing immunotherapy vulnerability in pancreatic cancer; the only recommendation for testing remains for patients with heritable cancers. Meanwhile high PD-L1 expression was correlated with poor prognosis. This association may identify a subgroup of patients where immune checkpoints inhibitors could provide therapeutic benefits, spotlighting the role of EUS-FNB in the field of immune-oncology.