Oestrogen receptor pathway activity is associated with outcome in endometrial cancer

Oestrogen receptor pathway activity is associated with outcome in endometrial cancer

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...

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Bibliographic Details
Published in:British journal of cancer Vol. 123; no. 5; pp. 785 - 792
Main Authors: van Weelden, Willem Jan, van der Putten, Louis J. M., Inda, Márcia A., van Brussel, Anne, Snijders, Marc P. L. M., Schriever, Lisanne M. M., Bulten, Johan, Massuger, Leon F. A. G., van de Stolpe, Anja, Pijnenborg, Johanna M. A.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-09-2020
Nature Publishing Group
Subjects:
631/67/1517/1931
631/67/327
692/53/2422
Aged
Aged, 80 and over
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Endometrioid - genetics
Carcinoma, Endometrioid - metabolism
Carcinoma, Endometrioid - pathology
Cohort Studies
DNA microarrays
Drug Resistance
Endometrial cancer
Endometrial Neoplasms - genetics
Endometrial Neoplasms - metabolism
Endometrial Neoplasms - pathology
Endometrium
Epidemiology
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Menstrual cycle
Middle Aged
Molecular Medicine
mRNA
Neoplasm Grading
Oncology
Paraffin
Precancerous Conditions - genetics
Precancerous Conditions - metabolism
Precancerous Conditions - pathology
Prognosis
Receptors, Estrogen - genetics
Receptors, Estrogen - metabolism
Receptors, Progesterone - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction
Uterine cancer
Uterus
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Summary: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.
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SourceType-Scholarly Journals-1
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content type line 23
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-020-0925-4