Cytologic testing for mismatch repair deficiency/microsatellite instability and NTRK gene fusion is not routinely indicated in primary pancreaticobiliary carcinoma cell block material
Year: 2024
Type: article
Study design: Observational Study
Abstract: Pancreaticobiliary carcinomas rarely harbor targetable genetic alterations, including microsatellite instability (MSI) or neurotrophic tyrosine receptor kinase ( NTRK ) gene fusions. As these malignancies are typically present at an advanced stage and have suboptimal response to chemotherapy, the discovery of an actionable genomic alteration provides an additional avenue of treatment for chemotherapy-refractory cases. In this study, we evaluate 319 cases of pancreaticobiliary carcinoma diagnosed on fine-needle aspiration biopsy or biliary brushing for DNA mismatch repair (MMR) protein deficiency and pan-TRK overexpression by immunohistochemistry (IHC) and compare these results to MSI and NTRK gene fusion molecular testing. Although we find a high concordance between MMR protein IHC and MSI molecular testing in the evaluation of MMR deficiency and between pan-TRK IHC and NTRK fusion testing by next-generation sequencing, the low prevalence of either of these genetic alterations in our cohort casts doubt on the value of screening cases of pancreaticobiliary carcinoma for MMR protein deficiency and NTRK fusions. • Though highly sensitive and specific, reflexive testing for MMR protein deficiency and NTRK gene fusions in pancreaticobiliary carcinomas should be reserved for treatment-resistant or unresectable cases. • This study reports high sensitivity and specificity for testing for MMR protein deficiency and NTRK gene fusions in pancreaticobiliary carcinoma. • When clinically indicated, MMR protein and pan-TRK immunostaining are efficient and inexpensive methods for evaluating pancreaticobiliary carcinomas.
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,850
OpenAlex ID: W4402038591