{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:05:07Z","timestamp":1784264707957,"version":"3.55.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thyroid nodules are extremely common, yet the exact physio-pathological mechanisms underlying their benign or malignant development remain poorly understood. Pentraxin-3 (PTX3) is an innate immune inflammatory mediator involved in inflammation, tissue remodeling, and oncogenesis, processes often coexistent in thyroid pathology. This study evaluated plasma and tissue PTX3 in patients undergoing thyroidectomy for benign or malignant nodules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 52 patients were enrolled. Plasma PTX3 levels were assessed by ELISA before surgery and again 45 days afterward. PTX3 expression, along with the abundance of two immune cell populations (e.g. macrophages and mast cells) was evaluated by immunohistochemistry using a tissue microarray.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Preoperative plasma PTX3 levels were significantly elevated (4.58 ng\/mL, p&amp;lt;0.05) compared with the normal reference range and declined significantly after surgery (3.58 ng\/mL, p&amp;lt;0.05). No significant differences in plasma PTX3 were observed between benign and malignant conditions. In tissue analysis, PTX3 expression was significantly elevated in malignant tissues relative to healthy thyroid counterparts, in which it was entirely absent; however, its overall expression levels remained low to moderate across most malignant samples. CD68 and tryptase showed variable patterns, with a higher abundance of macrophages and mast cells in carcinomas and a significant association between mast cell presence and thyroid cancer (p = 0.0025).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that increased PTX3 levels may indicate an active inflammatory response or tissue stress linked to thyroid nodular disease. Nevertheless, its specificity for distinguishing benign from malignant lesions has yet to be determined. Its strong local expression in thyroiditis and consistently low expression in most carcinomas further support the concept that the long pentraxin PTX3 plays an important role in innate immune activation and inflammation-driven thyroid tissue remodeling. Additional studies are needed to better define its potential prognostic value in thyroid carcinoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1847072","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:22:59Z","timestamp":1784262179000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pentraxin-3 in thyroid nodules: a systemic marker of pathology and a local mediator of inflammation and carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Miriam","family":"Cieri","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Pieve Emanuele, MI, Italy"]},{"name":"Department of Pathology, IRCCS Humanitas Research Hospital","place":["Rozzano, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Grizzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Pieve Emanuele, MI, Italy"]},{"name":"Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital","place":["Rozzano, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bottazzi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital","place":["Rozzano, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia Amy","family":"Rodda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Pieve Emanuele, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Petrillo","sequence":"additional","affiliation":[{"name":"Laboratory Analysis, Humanitas Mater Domini Clinical Institute","place":["Castellanza, VA, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital","place":["Rozzano, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Pasqualini","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital","place":["Rozzano, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Morenghi","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, IRCCS Humanitas Research Hospital","place":["Rozzano, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Zuliani","sequence":"additional","affiliation":[{"name":"General Surgery Department, Humanitas Mater Domini Clinical Institute","place":["Castellanza, VA, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Uccella","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Pieve Emanuele, MI, Italy"]},{"name":"Department of Pathology, IRCCS Humanitas Research Hospital","place":["Rozzano, MI, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"Chiari","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University","place":["Pieve Emanuele, MI, Italy"]},{"name":"General Surgery Department, Humanitas Mater Domini Clinical Institute","place":["Castellanza, VA, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1029926","article-title":"Mapping global epidemiology of thyroid nodules among general population: a systematic review and meta-analysis","volume":"12","author":"Mu","year":"2022","journal-title":"Front Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.5694\/mja17.01204","article-title":"Thyroid nodules: diagnosis and management","volume":"209","author":"Wong","year":"2018","journal-title":"Med J Aust"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2008.09.019","article-title":"Epidemiology of thyroid nodules","volume":"22","author":"Dean","year":"2008","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.endmts.2025.100255","article-title":"Update on thyroid nodules: characteristics and clinical management","volume":"19","author":"Lepore","year":"2025","journal-title":"Endocr Metab Sci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"696","DOI":"10.3803\/enm.2020.807","article-title":"Updates in the pathologic classification of thyroid neoplasms: a review of the World Health Organization classification","volume":"35","author":"Bai","year":"2020","journal-title":"Endocrinol Metab (Seoul)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2017","article-title":"PTX3, a humoral pattern recognition molecule, in innate immunity, tissue repair, and cancer","volume":"98","author":"Garlanda","year":"2018","journal-title":"Physiol Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra2206346","article-title":"Humoral innate immunity and acute-phase proteins","volume":"388","author":"Mantovani","year":"2023","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141268","article-title":"An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode","volume":"212","author":"Doni","year":"2015","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.004","article-title":"PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer","volume":"160","author":"Bonavita","year":"2015","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2026.1777246","article-title":"Diagnostic value and challenges in the immune regulation of pentraxin 3 in infectious diseases","volume":"17","author":"Shao","year":"2026","journal-title":"Front Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00794","article-title":"The long pentraxin PTX3 as a humoral innate immunity functional player and biomarker of infections and sepsis","volume":"10","author":"Porte","year":"2019","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1399","article-title":"Pentraxin-3 is a TSH-inducible protein in human fibrocytes and orbital fibroblasts","volume":"156","author":"Wang","year":"2015","journal-title":"Endocrinology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1146017","article-title":"The crossroad between autoimmune disorder, tissue remodeling and cancer of the thyroid: the long pentraxin 3 (PTX3)","volume":"14","author":"Chiari","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1211161","article-title":"Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation","volume":"370","author":"Cunha","year":"2014","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.02.015","article-title":"The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection","volume":"40","author":"Jaillon","year":"2014","journal-title":"Immunity"},{"key":"B16","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1084\/jem.20061301","article-title":"The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps","volume":"204","author":"Jaillon","year":"2007","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.s346058","article-title":"Identification of a four-gene signature for determining the prognosis of papillary thyroid carcinoma by integrated bioinformatics analysis","volume":"15","author":"Luo","year":"2022","journal-title":"Int J Gen Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1530\/endoabs.99.p164","article-title":"High local and systemic expression of pentraxin-3 in anaplastic thyroid cancer","volume":"26","author":"Bojoga","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41590-020-00832-x","article-title":"Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19","volume":"22","author":"Brunetta","year":"2021","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1426869","article-title":"PTX3 is expressed in terminal lymphatics and shapes their organization and function","volume":"15","author":"Doni","year":"2024","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7554\/elife.78601","article-title":"Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3","volume":"12","author":"Porte","year":"2023","journal-title":"Elife"},{"key":"B22","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s40164-023-00441-y","article-title":"The PTX3\/TLR4 autocrine loop as a novel therapeutic target in triple negative breast cancer","volume":"12","author":"Giacomini","year":"2023","journal-title":"Exp Hematol Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11091277","article-title":"Long pentraxin-3 follows and modulates bladder cancer progression","volume":"11","author":"Matarazzo","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2017.1333215","article-title":"Epigenetic regulation of the extrinsic oncosuppressor PTX3 gene in inflammation and cancer","volume":"6","author":"Rubino","year":"2017","journal-title":"Oncoimmunology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15179","article-title":"High PTX3 expression is associated with a poor prognosis in diffuse large B\u2010cell lymphoma","volume":"113","author":"Carreras","year":"2021","journal-title":"Cancer Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0244","article-title":"Follicular variant of papillary thyroid carcinoma: hybrid or mixture","volume":"26","author":"Daniels","year":"2016","journal-title":"Thyroid"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1847072\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:23:00Z","timestamp":1784262180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1847072\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":26,"alternative-id":["10.3389\/fendo.2026.1847072"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1847072","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"article-number":"1847072"}}