Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations
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.
Overview
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.
- Mismatch repair deficiency in about 0.8 percent of 833 pancreatic adenocarcinomas, most in Lynch syndrome carriers.
- Durable responses to PD-1 blockade in treated deficient cases.
- PCR-based MSI testing under-performs in pancreatic cancer; immunohistochemistry or sequencing is recommended.
Guidelines recommending universal mismatch repair testing in pancreatic cancer, by immunohistochemistry or sequencing rather than PCR alone, rest on this and similar series.
- Single-centre series with a small number of deficient cases.
- Frequency estimates vary between 0.5 and 2 percent across cohorts depending on the assay.
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