{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:48:20Z","timestamp":1787042900468,"version":"build-2736575974"},"reference-count":31,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Helsinki University Hospital Research Grants","award":["TYH2017138"],"award-info":[{"award-number":["TYH2017138"]}]},{"name":"Helsinki University Hospital Research Grants","award":["TYH20188223"],"award-info":[{"award-number":["TYH20188223"]}]},{"DOI":"10.13039\/100010135","name":"Finska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","award":["2018"],"award-info":[{"award-number":["2018"]}],"id":[{"id":"10.13039\/100010135","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Parathyroid carcinoma (PC) is extremely rare. Prognosis is poor, with no known evidence-based systemic therapies. We previously reported complete remission in a patient with metastasized parathyroid carcinoma and high tumor MGMT promoter methylation status who was treated with temozolomide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To study MGMT promoter methylation status in an additional set of aggressive parathyroid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design\/Setting<\/jats:title>\n                    <jats:p>The study included 12 patients: 7 with sporadic and 5 with familial primary hyperparathyroidism (two of the latter carried a CDC73 gross deletion). Patient 9 is the previously described patient with PC and high MGMT methylation status. Her daughter (patient 12) had surgery for severe primary hyperparathyroidism due to atypical parathyroid adenoma during pregnancy. Eleven patients thus had PC and one had atypical parathyroid adenoma. MGMT promoter methylation status was determined from DNA extracted from primary (n = 10) or metastatic (n = 2) tumors. A mean methylation level &gt;20% was considered high. Patient 11 had metastatic PC and received temozolomide cycles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Only the previously published patient (patient 9) had high tumor MGMT promoter methylation status. This was not a characteristic of the atypical parathyroid adenoma of the daughter (patient 12). Patient 11 (CDC73 intragenic deletion) has disseminated PC, low MGMT promoter methylation, and stable disease on follow-up after temozolomide treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>High MGMT promoter methylation status seems rare in PC. However, as demonstrated in other neuroendocrine tumors, some patients with disseminated PC might benefit from temozolomide. Demonstration of high methylation status could be a predictor of positive response to temozolomide treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/js.2019-00175","type":"journal-article","created":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T14:45:37Z","timestamp":1565189137000},"page":"2114-2122","source":"Crossref","is-referenced-by-count":12,"title":["MGMT Promoter Methylation and Parathyroid Carcinoma"],"prefix":"10.1210","volume":"3","author":[{"given":"Sara","family":"Storvall","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eeva","family":"Ryh\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Heiskanen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Vesterinen","sequence":"additional","affiliation":[{"name":"Department of Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank V","family":"Bensch","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Schildt","sequence":"additional","affiliation":[{"name":"HUS Medical Imaging Center, Department of Clinical Physiology and Nuclear Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soili","family":"Kyt\u00f6l\u00e4","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, HUSLAB, Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auli","family":"Karhu","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, HUSLAB, Helsinki University Hospital, Helsinki, Finland"},{"name":"Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland"},{"name":"Department of Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Arola","sequence":"additional","affiliation":[{"name":"Department of Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2428-0161","authenticated-orcid":false,"given":"Camilla","family":"Schalin-J\u00e4ntti","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"issue":"4","key":"2019103013432043400_bib1","first-page":"329","article-title":"Parathyroid cancer","volume":"4","author":"McClenaghan","year":"2015","journal-title":"Gland Surg"},{"issue":"7","key":"2019103013432043400_bib2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1080\/0284186X.2017.1306103","article-title":"A nationwide study on parathyroid carcinoma","volume":"56","author":"Ryh\u00e4nen","year":"2017","journal-title":"Acta Oncol"},{"issue":"9","key":"2019103013432043400_bib3","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1002\/cncr.22599","article-title":"Trends in the incidence and treatment of parathyroid cancer in the United States","volume":"109","author":"Lee","year":"2007","journal-title":"Cancer"},{"issue":"7-8","key":"2019103013432043400_bib4","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1445-2197.2010.05594.x","article-title":"Parathyroid carcinoma: increasing incidence and changing presentation","volume":"81","author":"Brown","year":"2011","journal-title":"ANZ J Surg"},{"issue":"8","key":"2019103013432043400_bib5","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1245\/s10434-010-1003-6","article-title":"Clinical presentation, staging and long-term evolution of parathyroid cancer","volume":"17","author":"Talat","year":"2010","journal-title":"Ann Surg Oncol"},{"issue":"9","key":"2019103013432043400_bib6","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1245\/s10434-018-6559-6","article-title":"Tumor size and presence of metastatic disease at diagnosis are associated with disease-specific survival in parathyroid carcinoma","volume":"25","author":"Lo","year":"2018","journal-title":"Ann Surg Oncol"},{"issue":"5","key":"2019103013432043400_bib7","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.surg.2014.05.014","article-title":"Prognostic factors and staging systems in parathyroid cancer: a multicenter cohort study","volume":"156","author":"Villar-del-Moral","year":"2014","journal-title":"Surgery"},{"issue":"6","key":"2019103013432043400_bib8","first-page":"1132","article-title":"Parathyroid carcinoma: biochemical and pathologic response to DTIC","volume":"96","author":"Calandra","year":"1984","journal-title":"Surgery"},{"issue":"11","key":"2019103013432043400_bib9","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1002\/cncr.11819","article-title":"Parathyroid carcinoma: is there a role for adjuvant radiation therapy","volume":"98","author":"Munson","year":"2003","journal-title":"Cancer"},{"issue":"9150","key":"2019103013432043400_bib10","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0140-6736(98)06469-1","article-title":"Control of hypercalcaemia of parathyroid carcinoma by immunisation","volume":"353","author":"Bradwell","year":"1999","journal-title":"Lancet"},{"issue":"4","key":"2019103013432043400_bib11","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1507\/endocrj.K09E-283","article-title":"First Japanese patient treated with parathyroid hormone peptide immunization for refractory hypercalcemia caused by metastatic parathyroid carcinoma","volume":"57","author":"Horie","year":"2010","journal-title":"Endocr J"},{"issue":"March","key":"2019103013432043400_bib12","first-page":"16-0113","article-title":"Diagnosis and treatment challenges of parathyroid carcinoma in a 27-year-old woman with multiple lung metastases","volume":"2017","author":"Rozhinskaya","year":"2017","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"issue":"4","key":"2019103013432043400_bib13","doi-asserted-by":"crossref","first-page":"e10114","DOI":"10.1002\/jbm4.10114","article-title":"Recurrent metastasized parathyroid carcinoma - long-term remission after combined treatments with surgery, radiotherapy, cinacalcet, zoledronic acid and temozolomide","volume":"3","author":"Storvall","year":"2018","journal-title":"JBMR Plus"},{"issue":"1","key":"2019103013432043400_bib14","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-17-0796","article-title":"European Society of Endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas","volume":"178","author":"Raverot","year":"2018","journal-title":"Eur J Endocrinol"},{"issue":"8","key":"2019103013432043400_bib15","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1530\/ERC-16-0117","article-title":"MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors","volume":"23","author":"Cros","year":"2016","journal-title":"Endocr Relat Cancer"},{"issue":"3","key":"2019103013432043400_bib16","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s12020-017-1474-3","article-title":"Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study","volume":"60","author":"Campana","year":"2018","journal-title":"Endocrine"},{"issue":"4","key":"2019103013432043400_bib17","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1158\/0008-5472.CAN-16-2983","article-title":"Temozolomide in the era of precision medicine","volume":"77","author":"Thomas","year":"2017","journal-title":"Cancer Res"},{"issue":"9","key":"2019103013432043400_bib18","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1210\/jc.2014-1481","article-title":"CDC73 intragenic deletion in familial primary hyperparathyroidism associated with parathyroid carcinoma","volume":"99","author":"Korpi-Hy\u00f6v\u00e4lti","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2019103013432043400_bib19","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S0039-6060(96)80101-2","article-title":"Parathyroid carcinoma in patients with chronic renal failure on maintenance hemodialysis","volume":"120","author":"Miki","year":"1996","journal-title":"Surgery"},{"issue":"1","key":"2019103013432043400_bib20","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s13277-015-4240-2","article-title":"MGMT testing allows for personalised therapy in the temozolomide era","volume":"37","author":"Dullea","year":"2016","journal-title":"Tumour Biol"},{"issue":"3","key":"2019103013432043400_bib21","doi-asserted-by":"crossref","first-page":"368","DOI":"10.2353\/jmoldx.2007.060167","article-title":"Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis","volume":"9","author":"Mikeska","year":"2007","journal-title":"J Mol Diagn"},{"issue":"00","key":"2019103013432043400_bib22","first-page":"1","article-title":"MGMT Testing in Glioblastomas","volume":"00","author":"Philteos","year":"2018","journal-title":"Am J Clin Oncol"},{"issue":"3","key":"2019103013432043400_bib23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s11060-009-0031-1","article-title":"Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods","volume":"97","author":"Karayan-Tapon","year":"2010","journal-title":"J Neurooncol"},{"issue":"3","key":"2019103013432043400_bib24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1001\/archoto.2007.50","article-title":"The role of pyrosequencing in head and neck cancer epigenetics","volume":"134","author":"Shaw","year":"2008","journal-title":"Arch Otolaryngol Head Neck Surg"},{"issue":"2","key":"2019103013432043400_bib25","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s11060-010-0307-5","article-title":"Determination of the methylation status of MGMT in different regions within glioblastoma multiforme","volume":"102","author":"Hamilton","year":"2011","journal-title":"J Neurooncol"},{"issue":"3","key":"2019103013432043400_bib26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11523-010-0153-6","article-title":"MGMT promoter methylation in malignant gliomas","volume":"5","author":"Riemenschneider","year":"2010","journal-title":"Target Oncol"},{"issue":"1","key":"2019103013432043400_bib27","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/jcp.25896","article-title":"The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials","volume":"233","author":"Binabaj","year":"2018","journal-title":"J Cell Physiol"},{"issue":"61","key":"2019103013432043400_bib28","doi-asserted-by":"crossref","first-page":"104046","DOI":"10.18632\/oncotarget.22001","article-title":"Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O6-methylguanine DNA methyltransferase as a biomarker for response","volume":"8","author":"Owen","year":"2017","journal-title":"Oncotarget"},{"issue":"10","key":"2019103013432043400_bib29","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1158\/1078-0432.CCR-06-2053","article-title":"Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors","volume":"13","author":"Ekeblad","year":"2007","journal-title":"Clin Cancer Res"},{"issue":"6","key":"2019103013432043400_bib30","doi-asserted-by":"crossref","first-page":"e92061","DOI":"10.1172\/jci.insight.92061","article-title":"Genomic profiling reveals mutational landscape in parathyroid carcinomas","volume":"2","author":"Pandya","year":"2017","journal-title":"JCI Insight"},{"issue":"3","key":"2019103013432043400_bib31","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1210\/js.2018-00043","article-title":"Comprehensive genomic characterization of parathyroid cancer identifies novel candidate driver mutations & core pathways","volume":"3","author":"Clarke","year":"2018","journal-title":"J Endocr Soc"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/js.2019-00175\/28969436\/js.2019-00175.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/3\/11\/2114\/30312457\/js.2019-00175.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/3\/11\/2114\/30312457\/js.2019-00175.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T15:12:52Z","timestamp":1572448372000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/3\/11\/2114\/5536615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,23]]},"references-count":31,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/js.2019-00175","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11]]},"published":{"date-parts":[[2019,7,23]]}}}