Targeted next-generation sequencing in the detection of mismatch repair deficiency in endometrial cancers.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
06
06
2018
accepted:
03
08
2018
revised:
27
07
2018
pubmed:
13
9
2018
medline:
18
12
2019
entrez:
13
9
2018
Statut:
ppublish
Résumé
Mismatch repair deficiency represents a biomarker of immunotherapy response and a phenotypic feature of Lynch syndrome-associated endometrial cancers. Using a targeted next-generation sequencing assay, we identified molecular features of mismatch repair deficiency, specifically insertion and deletion mutations in mononucleotide repeats, and established thresholds for the number of such mutations to classify endometrial cancers as mismatch repair deficient, proficient, or indeterminate. Sequencing classification was compared to the loss of MLH1, MSH2, MSH6, or PMS2 expression by immunohistochemistry. A total of 259 endometrial cancers were classified by sequencing as mismatch repair deficient (n = 48, 19%), proficient (n = 199, 77%), or indeterminate (n = 12, 5%). Sequencing findings were concordant with loss of expression of at least one mismatch repair protein in 47 of 48 (98%) cases classified as deficient and retained expression of all four proteins in 190 of 199 (95%) cases classified as proficient. Of the 12 cases classified as indeterminate, 7 (58%) demonstrated mismatch repair protein loss. Overall, targeted next-generation sequencing exhibited a high rate of concordance with immunohistochemistry for mismatch repair deficiency; however, sequencing was indeterminate in a few cases and demonstrated a false negative rate of 5%. Although we recommend implementation of a mismatch repair deficiency algorithm for laboratories performing next-generation sequencing cancer panels, immunohistochemistry remains a cost-effective screening method for mismatch repair deficiency in endometrial cancer.
Identifiants
pubmed: 30206407
doi: 10.1038/s41379-018-0125-4
pii: S0893-3952(22)00133-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
252-257Références
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