{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T04:12:04Z","timestamp":1772683924859,"version":"3.50.1"},"reference-count":157,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T00:00:00Z","timestamp":1603065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-016390: CANCEL STEM"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016390: CANCEL STEM"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-031438"],"award-info":[{"award-number":["POCI-01-0145-FEDER-031438"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PDTC\/MED_ONC\/31438\/2017"],"award-info":[{"award-number":["PDTC\/MED_ONC\/31438\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in benign lesions and in other subtypes of thyroid carcinomas. Thyroid calcifications are classified according to their diameter and location. At ultrasonography, microcalcifications appear as hyperechoic spots \u2264 1 mm in diameter and can be named as stromal calcification, bone formation, or psammoma bodies (PBs), whereas calcifications &gt; 1 mm are macrocalcifications. The mechanism of their formation is still poorly understood. Microcalcifications are generally accepted as a reliable indicator of malignancy as they mostly represent PBs. In order to progress in terms of the understanding of the mechanisms behind calcification occurring in thyroid tumors in general, and in PTC in particular, we decided to use histopathology as the basis of the possible cellular and molecular mechanisms of calcification formation in thyroid cancer. We explored the involvement of molecules such as runt-related transcription factor-2 (Runx-2), osteonectin\/secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteopontin (OPN) in the formation of calcification. The present review offers a novel insight into the mechanisms underlying the development of calcification in thyroid cancer.<\/jats:p>","DOI":"10.3390\/ijms21207718","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T09:36:28Z","timestamp":1603100188000},"page":"7718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Molecular Aspects of Thyroid Calcification"],"prefix":"10.3390","volume":"21","author":[{"given":"Luciana Bueno","family":"Ferreira","sequence":"first","affiliation":[{"name":"Cellular and Molecular Oncobiology Program, Research Coordination, National Institute of Cancer, Rua Andr\u00e9 Cavalcante n\u00ba 37, Rio de Janeiro 20231-050, Brazil"}]},{"given":"Etel","family":"Gimba","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Oncobiology Program, Research Coordination, National Institute of Cancer, Rua Andr\u00e9 Cavalcante n\u00ba 37, Rio de Janeiro 20231-050, Brazil"},{"name":"Natural Science Department, Health and Humanities Institute, Fluminense Federal University, Rua Recife, Rio das Ostras 28895-532, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0871-1427","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Vinagre","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, Porto 4200-319, Portugal"},{"name":"Cancer Signalling and Metabolism, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal"},{"name":"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (Ipatimup), Rua J\u00falio Amaral de Carvalho, Porto 4200-135, Portugal"}]},{"given":"Manuel","family":"Sobrinho-Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, Porto 4200-319, Portugal"},{"name":"Cancer Signalling and Metabolism, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal"},{"name":"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (Ipatimup), Rua J\u00falio Amaral de Carvalho, Porto 4200-135, Portugal"},{"name":"Departamento de Patologia, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Prof. Hern\u00e2ni Monteiro, Porto 4200-319, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-6998","authenticated-orcid":false,"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, Porto 4200-319, Portugal"},{"name":"Cancer Signalling and Metabolism, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal"},{"name":"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (Ipatimup), Rua J\u00falio Amaral de Carvalho, Porto 4200-135, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1089\/thy.2009.0110","article-title":"Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer","volume":"19","author":"Cooper","year":"2009","journal-title":"Thyroid"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1111\/j.1365-2362.2009.02162.x","article-title":"Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination","volume":"39","author":"Guth","year":"2009","journal-title":"Eur. 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