{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:29:00Z","timestamp":1763980140349,"version":"3.45.0"},"reference-count":27,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the European Joint Programme for Rare Disease under Research mobility","award":["EJP WP 17"],"award-info":[{"award-number":["EJP WP 17"]}]},{"name":"European Joint Programme for Rare Disease under Research mobility grant","award":["81\/15.11.2022","760067\/23\/5.2023"],"award-info":[{"award-number":["81\/15.11.2022","760067\/23\/5.2023"]}]},{"name":"the University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic inflammation plays a key role in cancer pathogenesis. Aggressive thyroid cancer is associated with immune infiltration and systemic inflammation. Long pentraxin 3 (PTX3) is an inflammatory protein implicated in tumor progression. This study evaluates PTX3 plasma levels in patients with non-medullary thyroid cancer (TC) compared to benign thyroid disease and investigates its tissue expression. We prospectively included 55 TC patients: 42 papillary, 3 follicular, 4 oncocytic, 4 anaplastic (ATC), and 2 poorly differentiated (PDTC). The control group consisted of 32 patients with benign thyroid disease. PTX3 plasma concentrations were measured by ELISA, and tissue expression of PTX3 and CD68 was analyzed using immunohistochemistry. PTX3 plasma levels did not significantly differ between TC and controls, but patients with PDTC and ATC had markedly higher concentrations. Tissue analysis showed strong PTX3 expression in three of four ATC cases in tumor and stromal cells, whereas benign and differentiated thyroid tissues exhibited minimal staining. CD68 expression was positive in ATC, indicating tumor-associated macrophage infiltration, but a few cells were double-positive for PTX3 and CD68. Our findings suggest a possible association between PTX3 and aggressive TC, particularly ATC. Further studies are needed to validate these findings and elucidate the cellular origin and functional role of PTX3.<\/jats:p>","DOI":"10.3390\/ijms262311335","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:24:17Z","timestamp":1763979857000},"page":"11335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High Local and Systemic Expression of Pentraxin-3 in Anaplastic Thyroid Cancer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6883-2378","authenticated-orcid":false,"given":"Andreea","family":"Bojoga","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-4140","authenticated-orcid":false,"given":"Pepijn","family":"van Houten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6994-493X","authenticated-orcid":false,"given":"Martin","family":"Jaeger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Rabold","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitte","family":"Walgreen","sequence":"additional","affiliation":[{"name":"Rheumatology Research Laboratory, Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liesbeth","family":"van Emst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dumitru","family":"Ioachim","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Institute of Endocrinology C. I. Parhon, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilse","family":"van Engen-van Grunsven","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-8125","authenticated-orcid":false,"given":"Corin","family":"Badiu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Endocrinology IV, National Institute of Endocrinology C. I. Parhon, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9603-0460","authenticated-orcid":false,"given":"Romana T.","family":"Netea-Maier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400129 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1245\/s10434-014-3545-5","article-title":"Anaplastic Thyroid Carcinoma: A 25-year Single-Institution Experience","volume":"21","author":"Mohebati","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1210\/jc.2012-1123","article-title":"Long-Term Surveillance of Papillary Thyroid Cancer Patients Who Do Not Undergo Postoperative Radioiodine Remnant Ablation: Is There a Role for Serum Thyroglobulin Measurement?","volume":"97","author":"Durante","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1677\/ERC-08-0036","article-title":"Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer","volume":"15","author":"Ryder","year":"2008","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00423-007-0251-9","article-title":"Serum levels of interleukin-1 receptor antagonist (IL-1ra) in thyroid cancer patients","volume":"393","author":"Kuzdak","year":"2008","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3892\/mco.2013.170","article-title":"Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer","volume":"1","author":"Suzuki","year":"2013","journal-title":"Mol. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1530\/ERC-17-0033","article-title":"Association of NF-\u03baB polymorphisms with clinical outcome of non-medullary thyroid carcinoma","volume":"24","author":"Plantinga","year":"2017","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_8","first-page":"13","article-title":"Reprogramming of myeloid cells and their progenitors in patients with non-medullary thyroid carcinoma","volume":"18","author":"Rabold","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Doni, A., Stravalaci, M., Inforzato, A., Magrini, E., Mantovani, A., Garlanda, C., and Bottazzi, B. (2019). The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00712"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"32817","DOI":"10.1074\/jbc.272.52.32817","article-title":"Multimer Formation and Ligand Recognition by the Long Pentraxin PTX3: Similarities and Differences with the Short Pentraxins C-Reactive Protein and Serum Amyloid P Component","volume":"272","author":"Bottazzi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbcan.2017.11.004","article-title":"Long pentraxin 3: A novel multifaceted player in cancer","volume":"1869","author":"Giacomini","year":"2018","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7741","DOI":"10.18632\/oncotarget.3482","article-title":"PTX3 gene activation in EGF-induced head and neck cancer cell metastasis","volume":"6","author":"Chang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e11780","DOI":"10.1097\/MD.0000000000011780","article-title":"Increased serum pentraxin-3 level predicts poor prognosis in patients with colorectal cancer after curative surgery, a cohort study","volume":"97","author":"Liu","year":"2018","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.4103\/0366-6999.189921","article-title":"Inhibitory Role of Pentraxin-3 in Esophageal Squamous Cell Carcinoma","volume":"129","author":"Ma","year":"2016","journal-title":"Chin. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Espinal-Enr\u00edquez, J., Mu\u00f1oz-Montero, S., Imaz-Rosshandler, I., Huerta-Verde, A., Mej\u00eda, C., and Hern\u00e1ndez-Lemus, E. (2015). Genome-wide expression analysis suggests a crucial role of dysregulation of matrix metalloproteinases pathway in undifferentiated thyroid carcinoma. BMC Genom., 16.","DOI":"10.1186\/s12864-015-1372-0"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1158\/1078-0432.CCR-10-3024","article-title":"Pentraxin-3 is a novel biomarker of lung carcinoma","volume":"17","author":"Diamandis","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.7150\/jca.25188","article-title":"Pentraxin 3 overexpression accelerated tumor metastasis and indicated poor prognosis in hepatocellular carcinoma via driving epithelial-mesenchymal transition","volume":"9","author":"Song","year":"2018","journal-title":"J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/ijc.29822","article-title":"Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients","volume":"138","author":"Infante","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jneuroim.2013.04.009","article-title":"The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas","volume":"260","author":"Locatelli","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1147","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":"ref_21","doi-asserted-by":"crossref","unstructured":"Chiari, D., Pirali, B., Perano, V., Leone, R., Mantovani, A., and Bottazzi, B. (2023). The crossroad between autoimmune disorder, tissue remodeling and cancer of the thyroid: The long pentraxin 3 (PTX3). Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1146017"},{"key":"ref_22","first-page":"270","article-title":"Clinical Significance of Erythrocyte Sedimentation Rate, Leukocyte, Fibrinogen, C-Reactive Protein, and Pentraxin 3 Values in Thyroid Nodules","volume":"56","author":"Destek","year":"2022","journal-title":"Med. Bull. Sisli Etfal Hosp."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/bjc.2013.348","article-title":"Clinical impact of pentraxin family expression on prognosis of pancreatic carcinoma","volume":"109","author":"Kondo","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_24","unstructured":"(2023, March 03). The Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/ENSG00000163661-PTX3\/cell+line."},{"key":"ref_25","first-page":"154495","article-title":"Inflammatory tumor microenvironment of thyroid cancer promotes cellular dedifferentiation and silencing of iodide-handling genes expression","volume":"246","author":"Zhang","year":"2023","journal-title":"Pathology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Brierley, J.D., Gospodarowicz, M.K., and Wittekind, C. (2016). TNM Classification of Malignant Tumours, Wiley Blackell. [8th ed.].","DOI":"10.1002\/9780471420194.tnmc26.pub3"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S2213-8587(13)70215-8","article-title":"Definition and management of radioactive iodine-refractory differentiated thyroid cancer","volume":"2","author":"Schlumberger","year":"2014","journal-title":"Lancet Diabetes Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:25:15Z","timestamp":1763979915000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":27,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311335"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311335","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]}}}