Oestrogen receptor pathway activity is associated with outcome in endometrial cancer.
Aged
Aged, 80 and over
Carcinoma, Endometrioid
/ genetics
Cohort Studies
Endometrial Neoplasms
/ genetics
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Neoplasm Grading
Precancerous Conditions
/ genetics
Prognosis
RNA, Messenger
/ genetics
Receptors, Estrogen
/ genetics
Receptors, Progesterone
/ metabolism
Signal Transduction
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
20
11
2019
accepted:
13
05
2020
revised:
22
04
2020
pubmed:
9
6
2020
medline:
1
4
2021
entrez:
9
6
2020
Statut:
ppublish
Résumé
Oestrogen receptor (ER) expression is a prognostic biomarker in endometrial cancer (EC). However, expression does not provide information about the functional activity of the ER pathway. We evaluated a model to quantify ER pathway activity in EC, and determined the prognostic relevance of ER pathway activity. ER pathway activity was measured in two publicly available datasets with endometrial and EC tissue, and one clinical cohort with 107 samples from proliferative and hyperplastic endometrium and endometrioid-type EC (EEC) and uterine serous cancer (USC). ER pathway activity scores were inferred from ER target gene mRNA levels from Affymetrix microarray data (public datasets), or measured by qPCR on formalin-fixed paraffin-embedded samples (clinical cohort) and related to ER expression and outcome. ER pathway activity scores differed significantly throughout the menstrual cycle supporting the validity of the pathway test. The highest ER pathway scores were found in proliferative and hyperplastic endometrium and stage I EEC, whereas stage II-IV EEC and USCs had significantly lower levels. Low ER pathway activity was associated with recurrent disease, and added prognostic value in patients with low ER expression. The ER pathway test reflects activity of the ER pathway, and may improve prediction of outcome in EC patients.
Sections du résumé
BACKGROUND
Oestrogen receptor (ER) expression is a prognostic biomarker in endometrial cancer (EC). However, expression does not provide information about the functional activity of the ER pathway. We evaluated a model to quantify ER pathway activity in EC, and determined the prognostic relevance of ER pathway activity.
METHODS
ER pathway activity was measured in two publicly available datasets with endometrial and EC tissue, and one clinical cohort with 107 samples from proliferative and hyperplastic endometrium and endometrioid-type EC (EEC) and uterine serous cancer (USC). ER pathway activity scores were inferred from ER target gene mRNA levels from Affymetrix microarray data (public datasets), or measured by qPCR on formalin-fixed paraffin-embedded samples (clinical cohort) and related to ER expression and outcome.
RESULTS
ER pathway activity scores differed significantly throughout the menstrual cycle supporting the validity of the pathway test. The highest ER pathway scores were found in proliferative and hyperplastic endometrium and stage I EEC, whereas stage II-IV EEC and USCs had significantly lower levels. Low ER pathway activity was associated with recurrent disease, and added prognostic value in patients with low ER expression.
CONCLUSION
The ER pathway test reflects activity of the ER pathway, and may improve prediction of outcome in EC patients.
Identifiants
pubmed: 32507853
doi: 10.1038/s41416-020-0925-4
pii: 10.1038/s41416-020-0925-4
pmc: PMC7463017
doi:
Substances chimiques
RNA, Messenger
0
Receptors, Estrogen
0
Receptors, Progesterone
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
785-792Références
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