{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:11:41Z","timestamp":1793823101843,"version":"4.6.1"},"reference-count":44,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2021-0283_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Reliable biological variation (BV) data are required for the clinical use of tumor markers in the diagnosis and monitoring of treatment effects in cancer. The European Biological Variation Study (EuBIVAS) was established by the EFLM Biological Variation Working Group to deliver BV data for clinically important measurands. In this study, EuBIVAS-based BV estimates are provided for cancer antigen (CA) 125, CA 15-3, CA 19-9, carcinoembryonic antigen, cytokeratin-19 fragment, alpha\u2010fetoprotein and human epididymis protein 4.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2021-0283_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Subjects from five European countries were enrolled in the study, and weekly samples were collected from 91 healthy individuals (53 females and 38 males; 21\u201369 years old) for 10 consecutive weeks. All samples were analyzed in duplicate within a single run. After excluding outliers and homogeneity analysis, the BVs of tumor markers were determined by CV-ANOVA on trend-corrected data, when relevant (R\u00f8raas method).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2021-0283_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Marked individuality was found for all tumor markers. CYFRA 21-1 was the measurand with the highest index of individuality (II) at 0.67, whereas CA 19-9 had the lowest II at 0.07. The CV<jats:sub>\n                        <jats:italic>I<\/jats:italic>\n                     <\/jats:sub>s of HE4, CYFRA 21-1, CA 19-9, CA 125 and CA 15-3 of pre- and postmenopausal females were significantly different from each other.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2021-0283_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study provides updated BV estimates for several tumor markers, and the findings indicate that marked individuality is characteristic. The use of reference change values should be considered when monitoring treatment of patients by means of tumor markers.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2021-0283","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:08:30Z","timestamp":1620778110000},"page":"543-552","source":"Crossref","is-referenced-by-count":33,"title":["Within- and between-subject biological variation data for tumor markers based on the European Biological Variation Study"],"prefix":"10.1515","volume":"60","author":[{"given":"Abdurrahman","family":"Co\u015fkun","sequence":"first","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , Italy"},{"name":"Department of Medical Biochemistry Atasehir , School of Medicine, Acibadem Mehmet Ali Ayd\u0131nlar University , Istanbul , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aasne K.","family":"Aarsand","sequence":"additional","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , Italy"},{"name":"Department of Medical Biochemistry and Pharmacology , Norwegian Porphyria Centre (NAPOS), Haukeland University Hospital , Bergen , Norway"},{"name":"Norwegian Organization for Quality Improvement of Laboratory Examinations (NOKLUS), Haraldsplass Deaconess Hospital , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sverre","family":"Sandberg","sequence":"additional","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , Italy"},{"name":"Department of Medical Biochemistry and Pharmacology , Norwegian Porphyria Centre (NAPOS), Haukeland University Hospital , Bergen , Norway"},{"name":"Norwegian Organization for Quality Improvement of Laboratory Examinations (NOKLUS), Haraldsplass Deaconess Hospital , Bergen , Norway"},{"name":"Department of Global Health and Primary Care , Faculty of Medicine, University of Bergen , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Guerra","sequence":"additional","affiliation":[{"name":"Servizio di Medicina di Laboratorio, Ospedale San Raffaele , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Servizio di Medicina di Laboratorio, Ospedale San Raffaele , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"D\u00edaz-Garz\u00f3n","sequence":"additional","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , Italy"},{"name":"Department of Laboratory Medicine , La Paz University Hospital , Milan , Italy"},{"name":"Analytical Quality Commission, Spanish Society of Laboratory Medicine (SEQCML) , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Fernandez-Calle","sequence":"additional","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , Italy"},{"name":"Department of Laboratory Medicine , La Paz University Hospital , Milan , Italy"},{"name":"Analytical Quality Commission, Spanish Society of Laboratory Medicine (SEQCML) , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0958-5354","authenticated-orcid":false,"given":"Ferruccio","family":"Ceriotti","sequence":"additional","affiliation":[{"name":"Central Laboratory, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Jonker","sequence":"additional","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , Italy"},{"name":"Certe, Wilhelmina Ziekenhuis Assen , Assen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , Italy"},{"name":"Blood Sciences, Ninewells Hospital & Medical School , Dundee , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Carobene","sequence":"additional","affiliation":[{"name":"EFLM Working Group on Biological Variation , Milan , Italy"},{"name":"EFLM Task Group for the Biological Variation Database , Milan , 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