Failure of immune checkpoint inhibitors for microsatellite instability-positive pancreatic adenocarcinoma with atypical pattern of short tandem repeat mutation.

ABSTRACT

Microsatellite instability (MSI) is an important biomarker in cancer. While routine methods can detect MSI in certain tumor types, in other tumor types the results may be incorrect due to differences in the MSI loci pattern. Here, we report the case of a patient with pancreatic adenocarcinoma, with confirmed MSI by two independent next-generation sequencing tests, but not by routine methods, who had progression on pembrolizumab. Comparison of the patient's MSI loci patterns with MSI+ colorectal adenocarcinoma samples showed a lower fraction of unstable loci, low resolution of a second peak in the repeat length spectrum of unstable short tandem repeats in the patient's sample, and a lower length of indels (3.7 vs 4.5 base pairs, p < 0.01).

Microsatellite instability (MSI) is typically evaluated to select patients who will most likely benefit from the treatments to make immune system work better (immunotherapy). MSI is difficult to identify in cancer, because its patterns can vary in different tumors. In this article, we describe a case of a pancreatic cancer patient whose tumor, although MSI-positive, did not respond to immunotherapy. We conclude that this can be because the MSI pattern was different from those typically observed in other cancers.