{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:41:31Z","timestamp":1771465291207,"version":"3.50.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Most low-grade, early-stage endometrial endometrioid carcinomas (EEC) have an excellent prognosis; however, recurrences occur in a small subset with several studies reporting an increase in <jats:italic toggle=\"yes\">CTNNB1<\/jats:italic> exon 3 mutations in this population. Herein we evaluated 10 recurrent low-grade (FIGO 1 or 2), early-stage (FIGO IA) EECs matched to 10 nonrecurrent EECs to further characterize their clinicopathologic features and molecular phenotype. Cases were matched to controls based on size, grade, and depth of invasion. All tumors were evaluated for specific clinicopathologic parameters followed by next-generation sequencing using a 1213 gene panel. Recurrent EECs demonstrated no significant clinicopathologic differences when compared with nonrecurrent EECs, in terms of age, body mass index, pattern of invasion, presence of endometrial atypical hyperplasia\/endometrioid intraepithelial neoplasia, associated metaplastic changes, peritumoral lymphocytes, mitoses, and tumor-infiltrating lymphocytes. Both cohorts also showed a similar number of pathogenic mutations, including <jats:italic toggle=\"yes\">CTNNB1<\/jats:italic> exon 3 mutations, as well as tumor mutational burden and microsatellite profiles. Although in this particular study, the lack of correlation between <jats:italic toggle=\"yes\">CTNNB1<\/jats:italic> exon 3 mutation and recurrence might be secondary to a small sample size, it also suggests the presence of other contributing factors. Thus, it helps set the foundation for larger series incorporating whole genome, transcriptome, proteome, and epigenome analyses to answer this clinically important question.<\/jats:p>","DOI":"10.1097\/pgp.0000000000000856","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:08:09Z","timestamp":1644192489000},"page":"26-34","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Clinicopathologic Evaluation and Molecular Profiling of Recurrent Stage IA Endometrial Endometrioid Carcinoma: A Case-control Study"],"prefix":"10.1097","volume":"42","author":[{"given":"Aarti E.","family":"Sharma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Moran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahana","family":"Somasegar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Steinhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Chapel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo R.","family":"Lastra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nita K.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren L.","family":"Ritterhouse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"R1-20250802","first-page":"7","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"R2-20250802","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1093\/jnci\/djab131","article-title":"Annual report to the nation on the status of cancer, part 1: national cancer statistics","volume":"113","author":"Islami","year":"2021","journal-title":"J Natl Cancer Inst"},{"issue":"suppl 1","key":"R3-20250802","first-page":"S105","article-title":"Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer","volume":"95","author":"Creasman","year":"2006","journal-title":"Int J Gynaecol Obstet"},{"key":"R4-20250802","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.ygyno.2003.11.048","article-title":"A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study","volume":"92","author":"Keys","year":"2004","journal-title":"Gynecol Oncol"},{"key":"R5-20250802","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma","volume":"497","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"R6-20250802","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/bjc.2015.190","article-title":"A clinically applicable molecular-based classification for endometrial cancers","volume":"113","author":"Talhouk","year":"2015","journal-title":"Br J Cancer"},{"key":"R7-20250802","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/cncr.30496","article-title":"Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer","volume":"123","author":"Talhouk","year":"2017","journal-title":"Cancer"},{"key":"R8-20250802","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ygyno.2014.06.010","article-title":"Beta-Catenin mutations in recurrent FIGO IA grade I endometrioid endometrial cancers","volume":"134","author":"Myers","year":"2014","journal-title":"Gynecol Oncol"},{"key":"R9-20250802","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/modpathol.2017.15","article-title":"CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence","volume":"30","author":"Kurnit","year":"2017","journal-title":"Mod Pathol"},{"key":"R10-20250802","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/PGP.0000000000000583","article-title":"Clinicopathologic and immunohistochemical correlates of CTNNB1 mutated endometrial endometrioid carcinoma","volume":"39","author":"Costigan","year":"2020","journal-title":"Int J Gynecol Pathol"},{"key":"R11-20250802","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ygyno.2019.03.100","article-title":"Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers","volume":"153","author":"Moroney","year":"2019","journal-title":"Gynecol Oncol"},{"key":"R12-20250802","doi-asserted-by":"crossref","first-page":"e30801","DOI":"10.1371\/journal.pone.0030801","article-title":"FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features","volume":"7","author":"Byron","year":"2012","journal-title":"PLoS One"},{"key":"R13-20250802","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1136\/ijgc-2020-001241","article-title":"Clinical patterns and genomic profiling of recurrent \u201cultra-low risk\u201d endometrial cancer","volume":"30","author":"Stasenko","year":"2020","journal-title":"Int J Gynecol Cancer"},{"key":"R14-20250802","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jmoldx.2016.07.012","article-title":"Clinical validation of a next-generation sequencing genomic oncology panel via cross-platform benchmarking against established amplicon sequencing assays","volume":"19","author":"Kadri","year":"2017","journal-title":"J Mol Diagn"},{"key":"R15-20250802","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/s41379-019-0298-5","article-title":"Quantitative next-generation sequencing-based analysis indicates progressive accumulation of microsatellite instability between atypical hyperplasia\/endometrial intraepithelial neoplasia and paired endometrioid endometrial carcinoma","volume":"32","author":"Chapel","year":"2019","journal-title":"Mod Pathol"},{"key":"R17-20250802","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ygyno.2006.02.011","article-title":"Follow-up after primary therapy for endometrial cancer: a systematic review","volume":"101","author":"Fung-Kee-Fung","year":"2006","journal-title":"Gynecol Oncol"},{"key":"R18-20250802","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1101\/gr.174789.114","article-title":"Exonuclease mutations in DNA polymerase epsilon reveal replication strand specific mutation patterns and human origins of replication","volume":"24","author":"Shinbrot","year":"2014","journal-title":"Genome Res"},{"key":"R19-20250802","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/path.5372","article-title":"Interpretation of somatic POLE mutations in endometrial carcinoma","volume":"250","author":"Leon-Castillo","year":"2020","journal-title":"J Pathol"},{"key":"R20-20250802","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/modpathol.2014.143","article-title":"Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations","volume":"28","author":"Hussein","year":"2015","journal-title":"Mod Pathol"},{"key":"R21-20250802","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/PGP.0000000000000243","article-title":"TP53 Mutational spectrum in endometrioid and serous endometrial cancers","volume":"35","author":"Schultheis","year":"2016","journal-title":"Int J Gynecol Pathol"},{"key":"R22-20250802","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41379-019-0220-1","article-title":"Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma","volume":"32","author":"Yano","year":"2019","journal-title":"Mod Pathol"},{"key":"R23-20250802","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ygyno.2016.07.090","article-title":"Molecular classification of endometrial carcinoma on diagnostic specimens is highly concordant with final hysterectomy: earlier prognostic information to guide treatment","volume":"143","author":"Talhouk","year":"2016","journal-title":"Gynecol Oncol"},{"key":"R24-20250802","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0090-8258(03)00126-4","article-title":"Survival after relapse in patients with endometrial cancer: results from a randomized trial","volume":"89","author":"Creutzberg","year":"2003","journal-title":"Gynecol Oncol"},{"key":"R25-20250802","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.3802\/jgo.2021.32.e22","article-title":"Recurrence risk factors in stage IA grade 1 endometrial cancer","volume":"32","author":"Nwachukwu","year":"2021","journal-title":"J Gynecol Oncol"},{"issue":"suppl 1","key":"R26-20250802","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1097\/PGP.0000000000000552","article-title":"Endometrial carcinoma, grossing and processing issues: recommendations of the International Society of Gynecologic Pathologists","volume":"38","author":"Malpica","year":"2019","journal-title":"Int J Gynecol Pathol"},{"key":"R27-20250802","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ygyno.2018.07.020","article-title":"Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: evaluation of the pilot phase of the PORTEC-4a trial","volume":"151","author":"Wortman","year":"2018","journal-title":"Gynecol Oncol"},{"key":"R28-20250802","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1136\/ijgc-2020-001929","article-title":"PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer","volume":"30","author":"van den Heerik","year":"2020","journal-title":"Int J Gynecol Cancer"}],"container-title":["International Journal of Gynecological Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/PGP.0000000000000856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T19:02:13Z","timestamp":1754161333000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/PGP.0000000000000856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,4]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1097\/pgp.0000000000000856","relation":{},"ISSN":["0277-1691"],"issn-type":[{"value":"0277-1691","type":"print"}],"subject":[],"published":{"date-parts":[[2022,2,4]]}}}