{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:30:58Z","timestamp":1772987458413,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072855"],"award-info":[{"award-number":["82072855"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472891"],"award-info":[{"award-number":["82472891"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203621"],"award-info":[{"award-number":["82203621"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gynecologic neuroendocrine carcinomas (NECs) are rare, highly aggressive malignancies with early metastatic potential and limited evidence to guide optimal management across different primary sites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To characterize the clinicopathological features, treatment patterns, survival outcomes, and prognostic factors of gynecologic NECs (cervix, endometrium, and ovary) treated at a single tertiary center over a 10\u2010year period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This observational, single\u2010center retrospective cohort study included patients diagnosed with gynecologic NEC at Women's Hospital, Zhejiang University School of Medicine, between January 2013 and August 2023. Clinicopathological data, treatment modalities, recurrence, and follow\u2010up outcomes were collected. Progression\u2010free survival (PFS) and overall survival (OS) were estimated using Kaplan\u2013Meier methods. Prognostic factors were assessed using log\u2010rank tests and multivariable Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 52 patients were identified, of whom 78.8% had cervical NEC. Primary surgery was performed in 90.4% of patients; adjuvant chemotherapy and radiotherapy were administered in 65.4% and 51.9%, respectively. Among cervical NEC cases with HPV testing, 69.7% were HPV16\/18\u2010positive. Immunohistochemical (IHC) showed high positivity for synaptophysin (95.3%) and chromogranin A (72.7%); Ki\u201067 exceeded 50% in 89.1% of evaluated cases. Median PFS for cervical NEC was 29 months; stage I cervical NEC showed a 5\u2010year PFS of 51.6% and 5\u2010year OS of 68.4%. Poorer prognosis was associated with FIGO stage \u2265\u2009IB3, mixed neuroendocrine\u2010non\u2010neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma, tumor size &gt;\u20094\u2009cm, and lymph node metastasis. On multivariable analysis of cervical NEC, MiNEN with squamous cell carcinoma remained an independent predictor of reduced PFS (HR\u2009=\u20096.97, 95% CI: 1.60\u201330.31;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Despite multimodal treatment, gynecologic NECs showed poor outcomes. The identification of MiNEN with squamous cell carcinoma as an independent adverse factor for PFS suggests histologic composition may meaningfully affect prognosis and warrants validation in larger, multicenter cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cervical NEC was the predominant subtype, most patients underwent surgery with adjuvant therapy, and survival was strongly stage\u2010dependent. MiNEN with squamous cell carcinoma independently predicted worse PFS, highlighting a potential high\u2010risk subgroup and reinforcing the need for multicenter prospective studies and more effective, potentially targeted treatment approaches for gynecologic NECs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71488","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T17:30:51Z","timestamp":1767202251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Retrospective Study on the Clinicopathological Characteristics and Prognostic Analysis of Gynecologic Neuroendocrine Carcinoma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1577-4548","authenticated-orcid":false,"given":"Yedan","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Gynecology and Oncology Women's Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"},{"name":"Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology  Zhejiang Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5047-7518","authenticated-orcid":false,"given":"Sen","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5254-3172","authenticated-orcid":false,"given":"Simin","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Oncology Women's Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-0775","authenticated-orcid":false,"given":"Junfen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Oncology Women's Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-022-09708-2"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.01.014"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2021.04.039"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2023.104201"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2011.04.011"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-4447-x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19910715)68:2<227::AID-CNCR2820680202>3.0.CO;2-I"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v12.i6.1111"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.15321"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.asjsur.2023.08.223"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2023-004708"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2023-005063"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2019.30.e103"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001042"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.04.001"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2321898121"},{"key":"e_1_2_12_18_1","first-page":"PO.19.00248","article-title":"Unique Genomic Landscape of High\u2010Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms","volume":"4","author":"Eskander R. 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