{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:05:18Z","timestamp":1790057118855,"version":"4.0.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neuroendocrine carcinoma (NEC) of the uterine cervix is a rare and aggressive malignancy for which disease-specific treatment strategies remain limited. Although immune checkpoint inhibitors (ICIs) have demonstrated activity in several cancers, PD-L1 expression in cervical NEC remains insufficiently characterized. This study descriptively evaluated PD-L1 expression patterns in cervical NEC using the PD-L1 IHC 22C3 pharmDx assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Six surgically resected cervical NEC specimens from Taiwanese women treated between 2010 and 2024 were retrospectively analyzed. PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx assay. TPS, CPS, and IC scores were evaluated descriptively; TC was also recorded but was numerically identical to TPS in all cases and is therefore reported jointly as TPS\/TC. Thresholds of TPS\/TC \u22651%, CPS \u22651, and IC \u22655% were used solely for exploratory analyses and were not interpreted as validated clinical cutoffs for cervical NEC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tumor-cell PD-L1 expression was uncommon, with TPS\/TC \u22651% observed in one case (16.7%). CPS \u22651 and IC \u22655% were each observed in three of six cases (50%). PD-L1 staining was more frequently observed in tumor-infiltrating immune cells than in tumor cells. One case demonstrated dual-compartment staining, with CPS 25, TPS\/TC 3%, and IC 30%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In this small cohort, PD-L1 expression was heterogeneous. Tumor-cell positivity by TPS\/TC was uncommon and largely limited to a single case, whereas PD-L1 staining was more frequently observed in immune cells. CPS and IC provided complementary descriptive information on PD-L1 distribution; however, their biological relevance and predictive value remain unvalidated in cervical NEC. Larger studies integrating molecular profiling, functional immune characterization, and clinical outcome data are needed to determine the potential clinical utility of PD-L1 assessment in this rare malignancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1933853","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:39:16Z","timestamp":1790055556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical profiling of PD-L1 expression in neuroendocrine carcinoma of the uterine cervix"],"prefix":"10.3389","volume":"17","author":[{"given":"Huang-Pin","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital","place":["Taichung, Taiwan"]},{"name":"Department of Obstetrics and Gynecology, Chung-Shan Medical University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Data Science and Big Data Analytics, Providence University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ru","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chung-Shan Medical University Hospital","place":["Taichung, Taiwan"]},{"name":"Department of Pathology, Chung-Shan Medical University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital","place":["Taichung, Taiwan"]},{"name":"Department of Obstetrics and Gynecology, Chung-Shan Medical University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chung-Shan Medical University Hospital","place":["Taichung, Taiwan"]},{"name":"Department of Pathology, Chung-Shan Medical University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Kuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Medicine, MacKay Memorial Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Biotechnology Medicine, MacKay Medical University","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Ping","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Medicine, MacKay Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gore.2025.101933","article-title":"Clinical outcomes of neuroendocrine carcinoma of the cervix: Retrospective review from a large academic cancer centre","volume":"61","author":"Fernandes","year":"2025","journal-title":"Gynecol Oncol Rep"},{"key":"B2","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1186\/s12885-018-4447-x","article-title":"Neuroendocrine carcinoma of the cervix: A systematic review of the literature","volume":"18","author":"Tempfer","year":"2018","journal-title":"BMC Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.02.008","article-title":"Natural history and outcome of neuroendocrine carcinoma of the cervix","volume":"141","author":"Margolis","year":"2016","journal-title":"Gynecol Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105123","article-title":"PD-1\/PD-L1 in cancer: Pathophysiological, diagnostic and therapeutic aspects","volume":"22","author":"Munari","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2026.01.006","article-title":"Immunology and therapeutic strategies in ovarian cancer","volume":"65","author":"Chang","year":"2026","journal-title":"Taiwan J Obstet Gynecol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.984896","article-title":"Immune checkpoint inhibitors in cervical cancer: Current status and research progress","volume":"12","author":"Xie","year":"2022","journal-title":"Front Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00473-5","article-title":"PD-L1 as a biomarker of response to immune-checkpoint inhibitors","volume":"18","author":"Doroshow","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B8","unstructured":"PD-L1 IHC 22C3 Pharmdx. 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