{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:14:02Z","timestamp":1760058842385,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Taiwan, R.O.C.","award":["MOST 105-2314-B-303-005","TCRD105-25"],"award-info":[{"award-number":["MOST 105-2314-B-303-005","TCRD105-25"]}]},{"name":"Hualien Tzu Chi Hospital, Hualien, Taiwan, R.O.C","award":["MOST 105-2314-B-303-005","TCRD105-25"],"award-info":[{"award-number":["MOST 105-2314-B-303-005","TCRD105-25"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To investigate the changes of ER\u03b1 and PRs in the epithelium and stroma of normal and neoplastic uterine cervix. Two pathologists independently scored the expression levels of ER\u03b1, PR(A+B), and PRB in the stroma and epithelium of normal, cervical intraepithelial neoplasia grade 2 and 3 (CIN2\/3), carcinoma in situ (CIS), and invasive cervical carcinoma (ICC) specimens. Sex hormone receptors were abundantly expressed in the stroma compared to the epithelium or carcinoma of the cervix. Stromal ER\u03b1 was progressively upregulated during cervical carcinogenesis, with an immunoreactive score (IRS) of 1.3 \u00b1 1.5, 2.1 \u00b1 1.9, and 3.6 \u00b1 3.3 in the CIN2\/3, CIS, and ICC groups, respectively (p &lt; 0.001). By contrast, epithelial PR(A+B) and PRB were downregulated, with IRS of 0.4 \u00b1 0.7 and 0.5 \u00b1 0.8, 0.1 \u00b1 0.4 and 0.2 \u00b1 0.6, and 0.1 \u00b1 0.6 and 0.1 \u00b1 0.4 in the CIN2\/3, CIS, and ICC groups, respectively (p &lt; 0.001). During the CIN2\/3 transition, the coexpression relationship between ER\u03b1 and PRs began to break down. Although epithelial PR(A+B) was downregulated, stromal PR(A+B) and PRB were upregulated with IRS of 2.0 \u00b1 2.0 and 2.0 \u00b1 1.9 as well as 2.1 \u00b1 2.3 and 3.2 \u00b1 3.2 in the CIS (p = 0.009) and ICC groups (p &lt; 0.001), respectively. After complete transformation, the stromal PRB was significantly upregulated, and its loss was related to more distant metastasis and poorer prognosis. The results of this study highlight the carcinogenic role of stromal ER\u03b1, the tumor suppressor role of epithelial PRs, and the importance of stromal PRB in the development of cervical cancer; they can be used as a basis for developing prevention and treatment strategies for this disease.<\/jats:p>","DOI":"10.3390\/ijms26094418","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T11:38:06Z","timestamp":1746531486000},"page":"4418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Topological Distribution of the Sex Hormone Receptor Expressions Highlights the Importance of Stromal ER\u03b1 and Epithelial PR in Malignant Transformation of the Uterine Cervix"],"prefix":"10.3390","volume":"26","author":[{"given":"Mun-Kun","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan"},{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Center for Prevention and Therapy of Gynecological Cancer, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen-Hung","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Hsun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9846-1571","authenticated-orcid":false,"given":"Cheng-Chuan","family":"Su","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Departments of Clinical Pathology and Anatomic Pathology, Dalin Tzu Chi Hospital, Dalin, Chiayi 62247, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9996-0428","authenticated-orcid":false,"given":"Chiu-Hsuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tang-Yuan","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan"},{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Center for Prevention and Therapy of Gynecological Cancer, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1002\/ijc.26250","article-title":"Time since first sexual intercourse and the risk of cervical cancer","volume":"130","author":"Plummer","year":"2012","journal-title":"Int. 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