Downregulation of FOXO1 mRNA levels predicts treatment failure in patients with endometrial pathology conservatively managed with progestin-containing intrauterine devices

Henry D Reyes; Matthew J Carlson; Eric J Devor; Yuping Zhang; Kristina W Thiel; Megan I Samuelson; Megan McDonald; Shujie Yang; Jean-Marie Stephan; Erica C Savage; Donghai Dai; Michael J Goodheart; Kimberly K Leslie

doi:10.1016/j.ygyno.2015.10.023

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Downregulation of FOXO1 mRNA levels predicts treatment failure in patients with endometrial pathology conservatively managed with progestin-containing intrauterine devices

Journal article

Peer reviewed

Downregulation of FOXO1 mRNA levels predicts treatment failure in patients with endometrial pathology conservatively managed with progestin-containing intrauterine devices

Henry D Reyes, Matthew J Carlson, Eric J Devor, Yuping Zhang, Kristina W Thiel, Megan I Samuelson, Megan McDonald, Shujie Yang, Jean-Marie Stephan, Erica C Savage, …

Gynecologic Oncology, Vol.140(1), pp.152-160

01/2016

DOI: 10.1016/j.ygyno.2015.10.023

PMCID: PMC4784706

PMID: 26524723

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Abstract

To examine hormone receptor expression levels and downstream gene activation in pre-treatment and post-treatment biopsies in a cohort of patients with endometrial pathology who were being conservatively managed with a progestin-containing intrauterine device (IUD). A molecular signature of treatment failure is proposed. A retrospective analysis of pre- and post-treatment biopsy specimens from 10 women treated with progestin-containing IUD for complex atypical hyperplasia (CAH) or grade 1 endometrioid adenocarcinoma was performed. Expression of estrogen receptor (ER), progesterone receptor (PR) and PR target genes was examined by immunohistochemistry (IHC) and quantitative RT-PCR. The mean treatment duration was 14.3months. Four CAH patients had stable disease or regressed after treatment, and four progressed to endometrioid adenocarcinoma. Both patients with an initial diagnosis of endometrioid adenocarcinoma regressed to CAH or no disease. In general, hormone receptor levels diminished post-treatment compared to pre-treatment biopsies; however, we noted unexpected higher expression of the B isoform of PR (PRB) as well as ER in those patients who progressed to frank cancer. There was a trend towards a non-nuclear cytoplasmic location of PRB in these patients. Importantly, the differentiating impact of PR signaling, as determined by the expression of the progestin-controlled tumor suppressor FOXO1, was lost in individuals who progressed on therapy. FOXO1 mRNA levels may serve as a biomarker for response to therapy and an indicator of PR function in patients being conservatively managed with a progestin-containing IUD. •We analyzed hormone receptor levels/activity following progestin-containing IUD.•PR target gene FOXO1 was significantly downregulated in patients who progressed.•FOXO1 mRNA levels may reflect PR function and response to progestin-based therapy.

Progestin-containing intrauterine devices

Endometrial hyperplasia

Endometrial cancer

Progesterone receptor

FOXO1

Details

Title: Subtitle: Downregulation of FOXO1 mRNA levels predicts treatment failure in patients with endometrial pathology conservatively managed with progestin-containing intrauterine devices
Creators: Henry D Reyes - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Matthew J Carlson - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Eric J Devor - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Yuping Zhang - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Kristina W Thiel - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Megan I Samuelson - Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Megan McDonald - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Shujie Yang - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Jean-Marie Stephan - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Erica C Savage - Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Donghai Dai - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Michael J Goodheart - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Kimberly K Leslie - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Gynecologic Oncology, Vol.140(1), pp.152-160
DOI: 10.1016/j.ygyno.2015.10.023
PMID: 26524723
PMCID: PMC4784706
NLM abbreviation: Gynecol Oncol
ISSN: 0090-8258
eISSN: 1095-6859
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: NIH, award: R01CA99908, R01CA184101, K12-HD063117; name: American Cancer Society Institutional Research Grant; name: Department of Obstetrics and Gynecology Research Development Fund
Language: English
Date published: 01/2016
Academic Unit: Pathology; Obstetrics and Gynecology
Record Identifier: 9983931819502771

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