{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:45:26Z","timestamp":1777365926196,"version":"3.51.4"},"reference-count":24,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"publisher","award":["DDHK 2004-3124"],"award-info":[{"award-number":["DDHK 2004-3124"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The ferritin-heavy chain (FTH1) is the catalytic subunit of the ferroxidase ferritin, which prevents oxidative DNA damage via intracellular iron storage. FTH1 was shown to be a prognostic marker for triple-negative breast cancer (BC) patients and associated with an enrichment of CD8+ effector T cells. However, whether the expression and localization of FTH1 are also associated with clinical outcome in other BC subtypes is unknown. Here, we investigated the association of FTH1 with time to survival in BCs from 222 BRCA1\/2 mutation carriers by immunohistochemistry on tissue microarrays. In addition, for 51 of these patients, the association between FTH1 and specific subsets of T cells was evaluated on whole slides using automatic scoring algorithms. We revealed that nuclear FTH1 (nFTH1) expression, in multivariable analyses, was associated with a shorter disease-free (HR = 2.71, 95% CI = 1.49\u20134.92, p = 0.001) and metastasis-free survival (HR = 3.54, 95% CI = 1.45\u20138.66, p = 0.006) in patients carrying a BRCA1\/2 mutation. However, we found no relation between cytoplasmic FTH1 expression and survival of BRCA1\/2 mutation carriers. Moreover, we did not detect an association between FTH1 expression and the amount of CD45+ (p = 0.13), CD8+ (p = 0.18), CD4+ (p = 0.20) or FOXP3+ cells (p = 0.17). Consequently, the mechanism underlying the worse recurrence-free survival of nFTH1 expression in BRCA1\/2 mutation carriers needs further investigation.<\/jats:p>","DOI":"10.3390\/cancers16010028","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T03:47:56Z","timestamp":1703044076000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression and Localization of Ferritin-Heavy Chain Predicts Recurrence for Breast Cancer Patients with a BRCA1\/2 Mutation"],"prefix":"10.3390","volume":"16","author":[{"given":"Shuoying","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Mieke","family":"Timmermans","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-6693","authenticated-orcid":false,"given":"Bernadette A. M.","family":"Heemskerk-Gerritsen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita M. A. C.","family":"Trapman-Jansen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9e","family":"Broeren-Foekens","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy J. C.","family":"Prager-van der Smissen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoesna","family":"El Hassnaoui","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6431-7467","authenticated-orcid":false,"given":"Tim","family":"van Tienhoven","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia K.","family":"Bes-Stobbe","sequence":"additional","affiliation":[{"name":"Pathan BV, Kleiweg 500, 3045 PM Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter J.","family":"Westenend","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, 3318 AL Dordrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolien H. M.","family":"van Deurzen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3428-3366","authenticated-orcid":false,"given":"John W. M.","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-0857","authenticated-orcid":false,"given":"Maartje J.","family":"Hooning","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-1966","authenticated-orcid":false,"given":"Antoinette","family":"Hollestelle","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.blre.2008.08.001","article-title":"Ferritin for the clinician","volume":"23","author":"Knovich","year":"2009","journal-title":"Blood Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.physiol.69.031905.164337","article-title":"Iron homeostasis","volume":"69","author":"Andrews","year":"2007","journal-title":"Annu. 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