Oncotarget

Research Papers:

Androgen receptor as potential therapeutic target in metastatic endometrial cancer

Ingvild Løberg Tangen, Therese Bredholt Onyango, Reidun Kopperud, Anna Berg, Mari K. Halle, Anne M. Øyan, Henrica M.J. Werner, Jone Trovik, Karl Henning Kalland, Helga B. Salvesen and Camilla Krakstad _

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Oncotarget. 2016; 7:49289-49298. https://doi.org/10.18632/oncotarget.10334

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Abstract

Ingvild Løberg Tangen1,2, Therese Bredholt Onyango1,2, Reidun Kopperud1,2, Anna Berg1,2, Mari K. Halle1,2, Anne M. Øyan3,4, Henrica M.J. Werner1,2, Jone Trovik1,2, Karl Henning Kalland3,4, Helga B. Salvesen1,2,*, Camilla Krakstad2,5,*

1Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Norway

2Department of Gynecology and Obstetrics, Haukeland University Hospital, Norway

3Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Norway

4Department of Microbiology, Haukeland University Hospital, Norway

5Centre for Cancer Biomarkers, Department of Biomedicine, University of Bergen, Norway

*These authors contributed equally to this work

Correspondence to:

Camilla Krakstad, email: camilla.krakstad@uib.no

Keywords: androgen receptor, endometrial cancer, biomarker, survival

Received: April 06, 2016     Accepted: June 13, 2016     Published: June 30, 2016

ABSTRACT

Purpose: The expression and involvement of estrogen (ER) and progesterone receptor (PR) is extensively studied in endometrial cancer. Androgen receptor (AR) is a hormone receptor less studied in female cancers, and we here aim to investigate the expression level of AR in endometrial cancer precursor lesions, primary tumors and metastases, and its potential as therapeutic target.

Results: Expression of AR was observed in 93% of hyperplasias, but only in 41% of non-endometrioid tumors. Compared to estrogen and progesterone receptor AR is more commonly expressed in metastatic lesions, and AR status is discordant in primary and metastatic lesions in a large proportion of cases. AR protein level was significantly associated with survival (P < 0.001), and a calculated AR to ERα ratio identified a subgroup of patients with particular poor outcome. The anti-androgen enzalutamide may have a growth inhibitory effect in endometrial cancer cells based on experiments with primary endometrial tumor cells.

Materials and Methods: 718 primary endometrial cancers and 298 metastatic lesions (from 142 patients) were investigated for expression of AR in relation to survival, clinical and histopathological data. Protein levels were investigated by immunohistochemistry and reverse phase protein array; mRNA levels by DNA oligonucleotide microarray. The effect of androgen stimulation and inhibition was tested on primary endometrial tumor cells.

Conclusions: A large proportion of metastatic endometrial cancer lesions express AR, which may be a potential target in these patients. Treatment targeting AR may be of particular benefit in patients with high AR levels compared to ERα levels.


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