Adoption of Universal Testing in Endometrial Cancers for Microsatellite Instability Using Next-Generation Sequencing.
JCO Precis Oncol
; 7: e2300033, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-37856764
ABSTRACT
PURPOSE:
To assess implementation of a next-generation sequencing (NGS) assay to detect microsatellite instability (MSI) as a screen for Lynch syndrome (LS) in endometrial cancer (EC), while determining and comparing characteristics of the four molecular subtypes.METHODS:
A retrospective review was performed of 408 total patients with newly diagnosed EC 140 patients who underwent universal screening with NGS and 268 patients who underwent screening via mismatch repair immunohistochemistry (MMR IHC) as part of a historical screening paradigm. In the NGS cohort, incidental POLE and TP53 mutations along with MSI were identified and used to characterize EC into molecular subtypes POLE-ultramutated, MSI high (MSI-H), TP53-mutated, and no specific molecular profile (NSMP). In historical cohorts, age- and/or family history-directed screening was performed with MMR IHC. Statistical analysis was performed using a t-test for continuous variables and chi-square or Fisher's exact test for categorical variables.RESULTS:
In the NGS cohort, 38 subjects (27%) had MSI-H EC, 100 (71%) had microsatellite stable EC, and two (1%) had an indeterminate result. LS was diagnosed in two subjects (1%), and all but five patients completed genetic screening (96%). Molecular subtypes were ascertained eight had POLE-ultramutated EC, 28 had TP53-mutated EC (20%), and 66 (47%) had NSMP. MSI-H and TP53-mutated EC had worse prognostic features compared with NSMP EC. Comparison with historical cohorts demonstrated a significant increase in follow-up testing after an initial positive genetic screen in the MSI NGS cohort (56% v 89%; P = .001).CONCLUSION:
MSI by NGS allowed for simultaneous screening for LS and categorization of EC into molecular subtypes with prognostic and therapeutic implications.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_muertes_prematuras_enfermedades_notrasmisibles
Asunto principal:
Neoplasias Colorrectales Hereditarias sin Poliposis
/
Neoplasias Endometriales
Límite:
Female
/
Humans
Idioma:
En
Revista:
JCO Precis Oncol
Año:
2023
Tipo del documento:
Article