{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T22:23:41Z","timestamp":1759703021033,"version":"3.37.3"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CD73 converts AMP to adenosine, an immunosuppressive metabolite that promotes tumorigenesis. This study presents a systematic evaluation of CD73 expression in benign, hyperplastic, and neoplastic thyroid. CD73 expression was assessed by immunohistochemistry in 142 thyroid samples. CD73 was expressed in normal thyroid (3\/6) and goiter (5\/6), with an apical pattern and mild intensity. Apical and mild CD73 expression was also present in oncocytic cell adenomas\/carcinomas (9\/10; 5\/8) and in follicular adenomas\/carcinomas (12\/18; 23\/27). In contrast, papillary thyroid carcinomas featured extensive and intense CD73 staining (49\/50) (vs. normal thyroid\/goiter, <jats:italic>p<\/jats:italic> &lt; 0.001). Seven of nine anaplastic carcinomas were CD73-positive with heterogeneous extensiveness of staining. Medullary and poorly differentiated carcinomas were mostly CD73-negative (1\/6; 2\/2). These results were corroborated by <jats:italic>NT5E<\/jats:italic> mRNA profiling. Papillary carcinomas feature enhanced CD73 protein and mRNA expression with distinct and intense staining, more pronounced in the invasive fronts of the tumors.<\/jats:p>","DOI":"10.1007\/s00428-021-03100-x","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T05:02:36Z","timestamp":1621573356000},"page":"209-214","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["CD73 expression in normal, hyperplastic, and neoplastic thyroid: a systematic evaluation revealing CD73 overexpression as a feature of papillary carcinomas"],"prefix":"10.1007","volume":"479","author":[{"given":"In\u00eas","family":"Monteiro","sequence":"first","affiliation":[]},{"given":"Edoardo","family":"Missiaglia","sequence":"additional","affiliation":[]},{"given":"Amedeo","family":"Sciarra","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Vasco","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Justine","family":"Bouilly","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Romero","sequence":"additional","affiliation":[]},{"given":"Christine","family":"Sempoux","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-516X","authenticated-orcid":false,"given":"Laurence","family":"de Leval","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"3100_CR1","doi-asserted-by":"publisher","first-page":"e23","DOI":"10.4110\/in.2019.19.e23","volume":"19","author":"S Arab","year":"2019","unstructured":"Arab S, Hadjati J (2019) Adenosine blockage in tumor microenvironment and improvement of cancer immunotherapy. Immune Netw 19:e23. https:\/\/doi.org\/10.4110\/in.2019.19.e23","journal-title":"Immune Netw"},{"key":"3100_CR2","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.trecan.2016.01.003","volume":"2","author":"L Antonioli","year":"2016","unstructured":"Antonioli L, Yegutkin GG, Pacher P, Blandizzi C, Hask\u00f3 G (2016) Anti-CD73 in cancer immunotherapy: awakening new opportunities. Trends in cancer 2:95\u2013109","journal-title":"Trends in cancer"},{"key":"3100_CR3","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","volume":"168","author":"P Sharma","year":"2017","unstructured":"Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A (2017) Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168:707\u2013723. https:\/\/doi.org\/10.1016\/j.cell.2017.01.017","journal-title":"Cell"},{"key":"3100_CR4","doi-asserted-by":"publisher","first-page":"925","DOI":"10.3389\/fimmu.2019.00925","volume":"10","author":"S Vigano","year":"2019","unstructured":"Vigano S, Alatzoglou D, Irving M, M\u00e9n\u00e9trier-Caux C, Caux C, Romero P, Coukos G (2019) Targeting adenosine in cancer immunotherapy to enhance T cell function. Front Immunol 10:925. https:\/\/doi.org\/10.3389\/fimmu.2019.00925","journal-title":"Front Immunol"},{"key":"3100_CR5","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1111\/j.1365-2559.2005.02277.x","volume":"48","author":"T Kondo","year":"2006","unstructured":"Kondo T, Nakazawa T, Murata S-I, Katoh R (2006) Expression of CD73 and its ecto-5\u2019-nucleotidase activity are elevated in papillary thyroid carcinomas. Histopathology 48:612\u2013614. https:\/\/doi.org\/10.1111\/j.1365-2559.2005.02277.x","journal-title":"Histopathology"},{"key":"3100_CR6","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s12307-018-0206-4","volume":"11","author":"APS Bertoni","year":"2018","unstructured":"Bertoni APS, de Campos RP, Tsao M, Braganhol E, Furlanetto TW, Wink MR (2018) Extracellular ATP is differentially metabolized on papillary thyroid carcinoma cells surface in comparison to normal cells. Cancer Microenviron 11:61\u201370. https:\/\/doi.org\/10.1007\/s12307-018-0206-4","journal-title":"Cancer Microenviron"},{"key":"3100_CR7","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.mce.2018.08.013","volume":"479","author":"APS Bertoni","year":"2019","unstructured":"Bertoni APS, Bracco PA, de Campos RP, Lutz BS, Assis-Brasil BM, Meyer ELS, Saffi J, Braganhol E, Furlanetto TW, Wink MR (2019) Activity of ecto-5\u2032-nucleotidase (NT5E\/CD73) is increased in papillary thyroid carcinoma and its expression is associated with metastatic lymph nodes. Mol Cell Endocrinol 479:54\u201360. https:\/\/doi.org\/10.1016\/j.mce.2018.08.013","journal-title":"Mol Cell Endocrinol"},{"key":"3100_CR8","doi-asserted-by":"publisher","unstructured":"Mastelic-Gavillet B, Navarro Rodrigo B, D\u00e9combaz L et al (2019) Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8+ T cells. J Immunotherapy Cancer 7(257). https:\/\/doi.org\/10.1186\/s40425-019-0719-5","DOI":"10.1186\/s40425-019-0719-5"},{"key":"3100_CR9","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.3390\/cancers12103042","volume":"12","author":"YM Jeong","year":"2020","unstructured":"Jeong YM, Cho H, Kim T-M, Kim Y, Jeon S, Bychkov A, Jung CK (2020) CD73 Overexpression promotes progression and recurrence of papillary thyroid carcinoma. Cancers 12:3042. https:\/\/doi.org\/10.3390\/cancers12103042","journal-title":"Cancers"},{"key":"3100_CR10","doi-asserted-by":"publisher","unstructured":"Kakudo K, Bychkov A, Bai Y et al (2018) The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives. Pathol Int pin.12737. https:\/\/doi.org\/10.1111\/pin.12737","DOI":"10.1111\/pin.12737"},{"key":"3100_CR11","doi-asserted-by":"publisher","unstructured":"\u00c1vila-Ibarra LR, Mora-Garc\u00eda M de L, Garc\u00eda-Rocha R, et al (2019) Mesenchymal stromal cells derived from normal cervix and cervical cancer tumors increase CD73 expression in cervical cancer cells through TGF-\u03b21 production. Stem Cells Dev 28:477\u2013488. doi:https:\/\/doi.org\/10.1089\/scd.2018.0183","DOI":"10.1089\/scd.2018.0183"},{"key":"3100_CR12","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s00262-018-2290-1","volume":"68","author":"A Sciarra","year":"2019","unstructured":"Sciarra A, Monteiro I, M\u00e9n\u00e9trier-Caux C, Caux C, Gilbert B, Halkic N, la Rosa S, Romero P, Sempoux C, de Leval L (2019) CD73 expression in normal and pathological human hepatobiliopancreatic tissues. Cancer Immunol Immunother 68:467\u2013478. https:\/\/doi.org\/10.1007\/s00262-018-2290-1","journal-title":"Cancer Immunol Immunother"},{"key":"3100_CR13","unstructured":"Gene Expression Omnibus https:\/\/www.ncbi.nlm.nih.gov\/geo\/. Accessed 3 Nov 2020"},{"key":"3100_CR14","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41419-017-0061-0","volume":"9","author":"MB Schaaf","year":"2018","unstructured":"Schaaf MB, Garg AD, Agostinis P (2018) Defining the role of the tumor vasculature in antitumor immunity and immunotherapy. Cell Death Dis 9:115. https:\/\/doi.org\/10.1038\/s41419-017-0061-0","journal-title":"Cell Death Dis"},{"key":"3100_CR15","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.3390\/cancers12113331","volume":"12","author":"A Gordon-Weeks","year":"2020","unstructured":"Gordon-Weeks A, Yuzhalin A (2020) Cancer extracellular matrix proteins regulate tumour immunity. Cancers 12:3331. https:\/\/doi.org\/10.3390\/cancers12113331","journal-title":"Cancers"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-021-03100-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-021-03100-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-021-03100-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T01:05:29Z","timestamp":1627002329000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-021-03100-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["3100"],"URL":"https:\/\/doi.org\/10.1007\/s00428-021-03100-x","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"type":"print","value":"0945-6317"},{"type":"electronic","value":"1432-2307"}],"subject":[],"published":{"date-parts":[[2021,5,21]]},"assertion":[{"value":"7 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the cantonal ethics committee on human research (Lausanne) (protocol PB_2017-00289) and is in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}