{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:25:45Z","timestamp":1768015545237,"version":"3.49.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH-C108-086, TSGH-C109094, and TSGH-D-110036"],"award-info":[{"award-number":["TSGH-C108-086, TSGH-C109094, and TSGH-D-110036"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A \u201chigh\u201d TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a \u201chigh\u201d score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p &lt; 0.001). A \u201chigh\u201d 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p &lt; 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11\u20130.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.<\/jats:p>","DOI":"10.1371\/journal.pone.0259330","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T17:32:02Z","timestamp":1635960722000},"page":"e0259330","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8593-7403","authenticated-orcid":true,"given":"Nien-Tzu","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7182-1031","authenticated-orcid":true,"given":"Cherng-Lih","family":"Perng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Ching","family":"Chou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pi-Shao","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Jia","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7356-446X","authenticated-orcid":true,"given":"Cheng-Chang","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Sheng","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8219-6382","authenticated-orcid":true,"given":"Tai-Kuang","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"pone.0259330.ref001","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1200\/JCO.2012.48.2596","article-title":"Type I and II endometrial cancers: have they different risk factors?","volume":"31","author":"VW Setiawan","year":"2013","journal-title":"J Clin Oncol"},{"key":"pone.0259330.ref002","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/1097-0142(19850715)56:2<403::AID-CNCR2820560233>3.0.CO;2-X","article-title":"The behavior of endometrial hyperplasia. 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