Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Cancer Med ; 12(16): 16707-16715, 2023 08.
Article in English | MEDLINE | ID: mdl-37376830

ABSTRACT

BACKGROUND: Microsatellite instability (MSI) occurs in several cancer types and is commonly used for prognosis and as a predictive biomarker for immune checkpoint therapy. METHODS: We analyzed n = 263 formalin-fixed paraffin-embedded (FFPE) tumor specimens (127 colorectal cancer (CRC), 55 endometrial cancer (EC), 33 stomach adenocarcinoma (STAD), and 48 solid tumor specimens of other tumor types) with a capillary electrophoresis based multiplex monomorphic marker MSI-PCR panel and an amplicon-based NGS assay for microsatellite instability (MSI+). In total, n = 103 (39.2%) cases with a known defect of the DNA mismatch repair system (dMMR), determined by a loss in protein expression of MSH2/MSH6 (n = 48, 46.6%) or MLH1/PMS2 (n = 55, 53.4%), were selected. Cases with an isolated loss of MSH6 or PMS2 were excluded. RESULTS: The overall sensitivity and specificity of the NGS assay in comparison with the MSI-PCR were 92.2% and 98.8%. With CRC cases a nearly optimal concordance was reached (sensitivity 98.1% and specificity 100.0%). Whereas EC cases only show a sensitivity of 88.6% and a specificity of 95.2%, caused by several cases with instability in less than five monomorphic markers, which could be difficult to analyze by NGS (subtle MSI+ phenotype). CONCLUSIONS: MSI analysis of FFPE DNA by NGS is feasible and the results show a high concordance in comparison with the monomorphic marker MSI-PCR. However, cases with a subtle MSI+ phenotype, most frequently manifest in EC, have a risk of a false-negative result by NGS and should be preferentially analyzed by capillary electrophoresis.


Subject(s)
Adenocarcinoma , Colorectal Neoplasms , Endometrial Neoplasms , Female , Humans , Microsatellite Instability , Mismatch Repair Endonuclease PMS2/metabolism , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Adenocarcinoma/genetics , Polymerase Chain Reaction , DNA Mismatch Repair/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Microsatellite Repeats , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...