Mutational profile of endometrial hyperplasia and risk of progression to endometrioid adenocarcinoma.
Adult
Aged
Carcinoma, Endometrioid
/ genetics
Class I Phosphatidylinositol 3-Kinases
/ genetics
DNA-Binding Proteins
/ genetics
Endometrial Hyperplasia
/ genetics
Endometrial Neoplasms
/ genetics
Female
High-Throughput Nucleotide Sequencing
Humans
Middle Aged
Mutation
PTEN Phosphohydrolase
/ genetics
Receptor, Fibroblast Growth Factor, Type 2
/ genetics
Retrospective Studies
Transcription Factors
/ genetics
Young Adult
endometrial cancer
endometrial hyperplasia
endometrial intraepithelial neoplasia
genetics
genomics
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
25
09
2019
revised:
03
01
2020
accepted:
28
01
2020
pubmed:
19
3
2020
medline:
10
4
2021
entrez:
19
3
2020
Statut:
ppublish
Résumé
Endometrial hyperplasia is a precursor to endometrioid adenocarcinoma (EMC), the most common uterine cancer. The likelihood of progression to carcinoma may be evaluated by histologic subclassification of endometrial hyperplasia, although these subclasses are subjective and only modestly reproducible among pathologists. Patient care would be improved by a more objective test to predict the risk of cancer progression. Next-generation sequencing was performed on archived endometrial biopsy specimens from a retrospective cohort of women with endometrial hyperplasia. Cases were considered to be either progressing if the patient subsequently developed EMC or resolving if the patient had a subsequent negative tissue sampling or no cancer during medium-term follow-up (32 patients: 15 progressing and 17 resolving). Somatic mutations in endometrial hyperplasia were assessed for enrichment in progressing cases versus resolving cases, with an emphasis on genes commonly mutated in EMC. Several mutations were more common in progressing hyperplasia than resolving hyperplasia, although significant overlap was observed between progressing and resolving cases. Mutations included those in PTEN, PIK3CA, and FGFR2, genes commonly mutated in EMC. Mutations in ARID1A and MYC were seen only in progressing hyperplasia, although these were uncommon; this limited diagnostic sensitivity. Progressing hyperplasia demonstrated an accumulation of mutations in oncogenic signaling pathways similarly to endometrial carcinoma. Because of mutational differences between progressing and nonprogressing hyperplasia, mutational analysis may predict the risk of progression from endometrial hyperplasia to EMC.
Sections du résumé
BACKGROUND
Endometrial hyperplasia is a precursor to endometrioid adenocarcinoma (EMC), the most common uterine cancer. The likelihood of progression to carcinoma may be evaluated by histologic subclassification of endometrial hyperplasia, although these subclasses are subjective and only modestly reproducible among pathologists. Patient care would be improved by a more objective test to predict the risk of cancer progression.
METHODS
Next-generation sequencing was performed on archived endometrial biopsy specimens from a retrospective cohort of women with endometrial hyperplasia. Cases were considered to be either progressing if the patient subsequently developed EMC or resolving if the patient had a subsequent negative tissue sampling or no cancer during medium-term follow-up (32 patients: 15 progressing and 17 resolving). Somatic mutations in endometrial hyperplasia were assessed for enrichment in progressing cases versus resolving cases, with an emphasis on genes commonly mutated in EMC.
RESULTS
Several mutations were more common in progressing hyperplasia than resolving hyperplasia, although significant overlap was observed between progressing and resolving cases. Mutations included those in PTEN, PIK3CA, and FGFR2, genes commonly mutated in EMC. Mutations in ARID1A and MYC were seen only in progressing hyperplasia, although these were uncommon; this limited diagnostic sensitivity. Progressing hyperplasia demonstrated an accumulation of mutations in oncogenic signaling pathways similarly to endometrial carcinoma.
CONCLUSIONS
Because of mutational differences between progressing and nonprogressing hyperplasia, mutational analysis may predict the risk of progression from endometrial hyperplasia to EMC.
Substances chimiques
ARID1A protein, human
0
DNA-Binding Proteins
0
Transcription Factors
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
FGFR2 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 2
EC 2.7.10.1
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2775-2783Informations de copyright
© 2020 American Cancer Society.
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