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. 2023 Sep 19;18(9):e0291361.
doi: 10.1371/journal.pone.0291361. eCollection 2023.

Androgen receptor and its correlation with estrogen and progesterone receptors, aimed for identification of cases for future anti-androgen therapy in endometrial cancers

Neda A Moatamed  1 , Saba Vahdatshariatpanahi  1 , David W Gjertson  1   2 , Chana R Sachs  1 , Yuna Kang  1 , Nora Ostrzega  1 , Jiaoti Huang  3 , Sanaz Memarzadeh  4   5   6   7   8
Affiliations

Androgen receptor and its correlation with estrogen and progesterone receptors, aimed for identification of cases for future anti-androgen therapy in endometrial cancers

Neda A Moatamed et al. PLoS One. .

Abstract

Introduction: The expression of androgen receptor (AR) is not commonly tested or studied in uterine cancers, unlike estrogen receptor (ER) and progesterone receptor (PR) which are positive in most endometrial carcinomas. In this series, we evaluated the expression of AR and its comparison to ER and PR in different types of endometrial cancers and have reviewed the literature.

Materials and methods: The status of AR, ER, and PR expression were evaluated in 71 cases which were categorized into endometrial endometrioid cancer (EEC), non-endometrioid endometrial cancers (NEEC), and metastatic carcinomas of endometrium. Expression of the receptors were compared to each other as well as to mismatch repair proteins (MMR), p53, and body mass index (BMI) using Fisher's Exact test in the StatPlus software.

Results: In EECs, the positivity was 97% for all the three receptors. In NEEC, positivity rates were 68%, 48%, and 35% for AR, ER, and PR respectively. In Metastatic carcinomas, AR and ER positivity was seen in 100% while PR was positive in 75% of the cases. In all cancers, the rates were 17% (11/66) for MMR loss, 57% (30/53) for p53 aberrant expression, and 76% (54/71) for the patients with BMI of ≥ 25 (kg/m2).

Conclusion: AR is expressed in a high percentage of endometrial cancers. Its significance is more evident in high-grade NEEC where ER and PR may not be expressed. These findings warrant further evaluation of AR expression and candidacy of this pathway as a potential therapeutic target in endometrial cancers.

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Conflict of interest statement

Authors have no competing interests.

Figures

Fig 1
Fig 1. Androgen, estrogen, and progesterone receptors in endometrioid carcinoma.
Hematoxylin and eosin (H&E) stain of a case (case #30, S1 Table) of uterine endometrioid carcinoma showing glandular proliferation, composed of columnar cells with pseudostratified nuclei and mild to moderate atypia. The corresponding androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) immunostains show similar positive nuclear staining of the malignant cells (10× objective).
Fig 2
Fig 2. Androgen, estrogen, and progesterone receptors in serous carcinoma.
Hematoxylin and eosin (H&E) stain of a case of uterine serous carcinoma showing papillary and glandular patterns where cells exhibit high-grade cytology, mitotic figure, and marked nuclear pleomorphism (case #40, S1 Table). The corresponding androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) immunostains show positive nuclear staining with AR and negative nuclear staining of the malignant cells for ER and PR (40× objective).
Fig 3
Fig 3. Androgen, estrogen, and progesterone receptors in clear cell carcinoma.
Hematoxylin and eosin (H&E) stain of a case of clear cell carcinoma of the endometrium showing tubulocystic and solid architectural patterns, variably pleomorphic and cuboidal cells, and clear cytoplasm (case #53, S1 Table). The corresponding androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) immunostains show positive nuclear staining for AR and negative staining of the malignant cells for ER and PR (40× objective).
Fig 4
Fig 4. Androgen, estrogen, and progesterone receptors in carcinosarcoma.
Hematoxylin and eosin (H&E) stain of a case of uterine carcinosarcoma showing a biphasic pattern composed of high-grade carcinomatous and sarcomatous components (case #60, S1 Table). The corresponding androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) immunostains show positive nuclear staining for AR in both carcinomatous and sarcomatous components. ER and PR are negative in the two components of the cancer (20× objective).
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