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Of more than 800 pancreatic cancers sequenced at one centre, under one in a hundred were mismatch repair deficient, most in people with Lynch syndrome, and several responded to immunotherapy. The paper set out how to test for the abnormality reliably in a cancer where standard tests often mislead.
Analysis of 833 pancreatic ductal adenocarcinomas sequenced with the MSK-IMPACT panel at Memorial Sloan Kettering, using MSIsensor scoring with immunohistochemistry and germline testing to identify mismatch repair deficiency. Deficiency was found in about 0.8 percent of tumours, most of them in patients with Lynch syndrome, and several treated with anti-PD-1 therapy had durable responses.
The authors show that low tumour cellularity and the desmoplastic stroma of pancreatic cancer make PCR-based microsatellite instability testing unreliable and recommend immunohistochemistry or sequencing-based assays with germline follow-up.
Guidelines recommending universal mismatch repair testing in pancreatic cancer, by immunohistochemistry or sequencing rather than PCR alone, rest on this and similar series.
Shares KEYNOTE-158, MSI and mismatch-repair testing, dMMR (mismatch repair deficiency by IHC), MSI-high (microsatellite instability by PCR or sequencing).
Shares MSH2, dMMR (mismatch repair deficiency by IHC), MSI-high (microsatellite instability by PCR or sequencing), Lynch syndrome.
Shares MSH6, MSH2, MSI-high (microsatellite instability by PCR or sequencing), Lynch syndrome.
Shares MLH1, MSI and mismatch-repair testing, dMMR (mismatch repair deficiency by IHC), Lynch syndrome.
Shares KEYNOTE-158, dMMR (mismatch repair deficiency by IHC), MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma.