{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T02:11:21Z","timestamp":1793844681956,"version":"4.6.1"},"reference-count":72,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["SEBCATP-2023\/100008"],"award-info":[{"award-number":["SEBCATP-2023\/100008"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["CTRQQR-2021\\100009"],"award-info":[{"award-number":["CTRQQR-2021\\100009"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Trace metal homeostasis is critical for cellular function and often disrupted in diseases such as cancer. Spatially resolved techniques enable mapping of metal distributions within complex cellular environments, surpassing the limitations of bulk analyses. Formalin-fixed, paraffin-embedded (FFPE) tissues are widely used in research, yet the impact of FFPE processing on endogenous elemental contents and distributions remains unclear, with conflicting findings across sample types. This study evaluates the suitability of FFPE human breast carcinoma tissue sections for multielemental bioimaging by direct comparison with paired fresh frozen (FF) tissues and assesses potential sources of contamination or elemental losses during processing. Three FF human breast carcinoma specimens were bisected and processed as either FF or FFPE. Serial sections underwent analyses by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), alongside hematoxylin and eosin (H&amp;E)-staining, to compare elemental profiles in whole sections and morphologically distinct regions. In parallel, FFPE processing reagents encompassing tissue-marking dyes, formalin, paraffin wax, xylene, and ethanol were analyzed via solution ICP-MS to contextualize the in situ findings. The multielemental imaging results revealed that Zn, Mn, and Fe were largely preserved in FFPE sections, supporting the continued use of such tissues for in situ metal analyses. Addition of Cu was observed for all FFPE samples, most likely caused by exposure to blue tissue-marking dye. Formalin induced variable elemental leaching, most notably affecting Mg. Paraffin wax, ethanol, and xylene contained minimal trace metal levels both before and after contact with tissues.<\/jats:p>","DOI":"10.1021\/cbmi.5c00217","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T05:22:22Z","timestamp":1770182542000},"page":"1390-1404","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Histological\nProcessing on Endogenous Elemental\nContents and Distributions in Breast Cancer Tissue Sections"],"prefix":"10.1021","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4079-942X","authenticated-orcid":true,"given":"Amy V.","family":"Lovejoy","sequence":"first","affiliation":[{"name":"Imperial College London , , ,","place":["London, U.K., SW7 2AZ"]},{"name":"Institute of Cancer Research , , ,","place":["Sutton, U.K., SM2 5NG"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-5846","authenticated-orcid":true,"given":"Alexander P.","family":"Morrell","sequence":"additional","affiliation":[{"name":"King\u2019s College London , , ,","place":["London, U.K., SE1 9NH"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2417-9821","authenticated-orcid":true,"given":"Diego","family":"Mesa","sequence":"additional","affiliation":[{"name":"Imperial College London , , ,","place":["London, U.K., SW7 2AZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6772-2054","authenticated-orcid":true,"given":"Alex","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Imperial College London , , ,","place":["London, U.K., SW7 2AZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1380-9047","authenticated-orcid":true,"given":"Piotr R.","family":"Golda","sequence":"additional","affiliation":[{"name":"King\u2019s College London , , ,","place":["London, U.K., SE1 9NH"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay L.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Charing Cross Hospital Campus , , ,","place":["London, U.K., W6 8RP"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3361-0274","authenticated-orcid":true,"given":"Evie","family":"Wren","sequence":"additional","affiliation":[{"name":"Charing Cross Hospital Campus , , ,","place":["London, U.K., W6 8RP"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8913-7924","authenticated-orcid":true,"given":"Katharina","family":"Kreissig","sequence":"additional","affiliation":[{"name":"Imperial College London , , ,","place":["London, U.K., SW7 2AZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-1100","authenticated-orcid":true,"given":"Charles","family":"Coombes","sequence":"additional","affiliation":[{"name":"Imperial College London , , ,","place":["London, U.K., W12 0NN"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-9872","authenticated-orcid":true,"given":"Mark","family":"Rehka\u0308mper","sequence":"additional","affiliation":[{"name":"Imperial College London , , ,","place":["London, U.K., SW7 2AZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9056-8980","authenticated-orcid":true,"given":"Rebekah E.T.","family":"Moore","sequence":"additional","affiliation":[{"name":"Imperial College London , , ,","place":["London, U.K., SW7 2AZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"2026073101214024700_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110173","article-title":"Essential metals in\nhealth and disease","volume":"367","author":"Jomova","year":"2022","journal-title":"Chemico-Biological Interactions"},{"issue":"1","key":"2026073101214024700_cit2","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1021\/pr050361j","article-title":"Counting the zinc-proteins\nencoded in the human genome","volume":"5","author":"Andreini","year":"2006","journal-title":"J. Proteome Res."},{"issue":"4","key":"2026073101214024700_cit3","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1083\/jcb.200702081","article-title":"Zinc is a novel intracellular\nsecond messenger","volume":"177","author":"Yamasaki","year":"2007","journal-title":"J. Cell Biol."},{"issue":"8","key":"2026073101214024700_cit4","doi-asserted-by":"publisher","first-page":"11675","DOI":"10.1007\/s11356-021-16549-9","article-title":"Association between trace elements in cancerous and\nnon-cancerous tissues with the risk of breast cancers in western Iran","volume":"29","author":"Mansouri","year":"2022","journal-title":"Environmental Science and Pollution Research"},{"issue":"7","key":"2026073101214024700_cit5","doi-asserted-by":"publisher","DOI":"10.1093\/mtomcs\/mfac037","article-title":"Recent advances in the application\nof metallomics in diagnosis and prognosis of human cancer","volume":"14","author":"Zhang","year":"2022","journal-title":"Metallomics"},{"issue":"3","key":"2026073101214024700_cit6","doi-asserted-by":"publisher","first-page":"778","DOI":"10.3390\/ijms20030778","article-title":"The metallome of lung cancer and\nits potential use as biomarker","volume":"20","author":"Callejo\u0301n-Leblic","year":"2019","journal-title":"International\nJournal of Molecular Sciences"},{"issue":"1","key":"2026073101214024700_cit7","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s40364-021-00345-1","article-title":"Structures and biological\nfunctions of zinc finger proteins and their roles in hepatocellular\ncarcinoma","volume":"10","author":"Li","year":"2022","journal-title":"Biomarker Research"},{"issue":"1","key":"2026073101214024700_cit8","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12929-016-0269-9","article-title":"Zinc finger proteins\nin cancer progression","volume":"23","author":"Jen","year":"2016","journal-title":"Journal of Biomedical\nScience"},{"issue":"3","key":"2026073101214024700_cit9","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/s41419-019-1335-5","article-title":"ZFP57 suppress proliferation\nof breast cancer cells through down-regulation\nof MEST-mediated Wnt\/\u03b2-catenin signalling pathway","volume":"10","author":"Chen","year":"2019","journal-title":"Cell Death & Disease"},{"issue":"6","key":"2026073101214024700_cit10","doi-asserted-by":"publisher","DOI":"10.1093\/mtomcs\/mfab027","article-title":"Zinc stable\nisotope analysis reveals Zn dyshomeostasis in benign tumours, breast\ncancer, and adjacent histologically normal tissue","volume":"13","author":"Sullivan","year":"2021","journal-title":"Metallomics"},{"issue":"1","key":"2026073101214024700_cit11","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1039\/C4MT00260A","article-title":"Zinc isotopic compositions of breast cancer tissue","volume":"7","author":"Larner","year":"2015","journal-title":"Metallomics"},{"issue":"1","key":"2026073101214024700_cit12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40164-022-00363-1","article-title":"Breast cancer\nheterogeneity and its implication in personalized precision therapy","volume":"12","author":"Guo","year":"2023","journal-title":"Experimental Hematology & Oncology"},{"issue":"5","key":"2026073101214024700_cit13","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1111\/his.13642","article-title":"Breast cancer intratumour\nheterogeneity: current status\nand clinical implications","volume":"73","author":"Joseph","year":"2018","journal-title":"Histopathology"},{"issue":"6","key":"2026073101214024700_cit14","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s10552-016-0746-1","article-title":"In situ clinical evidence that zinc levels are decreased\nin breast invasive ductal carcinoma","volume":"27","author":"Costello","year":"2016","journal-title":"Cancer\nCauses & Control"},{"issue":"8","key":"2026073101214024700_cit15","doi-asserted-by":"publisher","DOI":"10.1093\/mtomcs\/mfac052","article-title":"Quantitative multiplexed analysis of MMP-11 and CD45\nin metastatic breast cancer tissues by immunohistochemistry-assisted\nLA\u2013ICP\u2013MS","volume":"14","author":"Johnson","year":"2022","journal-title":"Metallomics"},{"issue":"1","key":"2026073101214024700_cit16","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1039\/C8MT00235E","article-title":"Across\nthe spectrum: integrating multidimensional metal analytics for in\nsitu metallomic imaging","volume":"11","author":"Stewart","year":"2019","journal-title":"Metallomics"},{"key":"2026073101214024700_cit17","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12943-015-0486-y","article-title":"Subtype-specific\naccumulation of\nintracellular zinc pools is associated with the malignant phenotype\nin breast cancer","volume":"15","author":"Chandler","year":"2016","journal-title":"Molecular Cancer"},{"issue":"1","key":"2026073101214024700_cit18","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s00404-020-05789-8","article-title":"Zinc distribution within\nbreast cancer tissue of different intrinsic\nsubtypes","volume":"303","author":"Rusch","year":"2021","journal-title":"Archives of Gynecology and Obstetrics"},{"issue":"1","key":"2026073101214024700_cit19","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1039\/D2JA00295G","article-title":"Characterization of a high-sensitivity ICP-TOFMS instrument\nfor microdroplet, nanoparticle, and microplastic analyses","volume":"38","author":"Harycki","year":"2023","journal-title":"Journal of Analytical Atomic Spectrometry"},{"issue":"1","key":"2026073101214024700_cit20","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1002\/mas.20239","article-title":"Bioimaging of metals\nby laser ablation\ninductively coupled plasma mass spectrometry (LA-ICP-MS)","volume":"29","author":"Becker","year":"2010","journal-title":"Mass Spectrom. Rev."},{"issue":"1","key":"2026073101214024700_cit21","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s00216-021-03357-w","article-title":"Micro-droplet-based\ncalibration for quantitative elemental bioimaging by LA-ICPMS","volume":"414","author":"Schweikert","year":"2022","journal-title":"Anal. Bioanal. Chem."},{"issue":"1","key":"2026073101214024700_cit22","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00216-019-02195-1","article-title":"Calibration strategies\nfor elemental analysis of biological\nsamples by LA-ICP-MS and LIBS \u2013 A review","volume":"412","author":"Martinez","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"issue":"11","key":"2026073101214024700_cit23","first-page":"436","article-title":"Formalin pigment\n(acid hematin) and related pigments","volume":"42","author":"Pizzolato","year":"1976","journal-title":"Am. J.\nMed. Technol."},{"key":"2026073101214024700_cit24","first-page":"225","article-title":"Chapter\nfifteen - Preparation of formalin-fixed paraffin-embedded tissue for\nimmunohistochemistry","volume-title":"Methods in Enzymology","author":"Canene-Adams","year":"2013"},{"issue":"6","key":"2026073101214024700_cit25","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1177\/39.6.1709656","article-title":"Antigen retrieval in formalin-fixed,\nparaffin-embedded tissues: an enhancement method for immunohistochemical\nstaining based on microwave oven heating of tissue sections","volume":"39","author":"Shi","year":"1991","journal-title":"Journal of Histochemistry & Cytochemistry"},{"issue":"1","key":"2026073101214024700_cit26","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2121-9-13","article-title":"Multiple immunofluorescence\nlabelling of formalin-fixed paraffin-embedded (FFPE) tissue","volume":"9","author":"Robertson","year":"2008","journal-title":"BMC Cell Biology"},{"issue":"9","key":"2026073101214024700_cit27","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1002\/ijc.34620","article-title":"Clonal expansion of\nintra-epithelial T cells in breast cancer revealed by spatial transcriptomics","volume":"153","author":"Romanens","year":"2023","journal-title":"Int. J. Cancer"},{"issue":"3","key":"2026073101214024700_cit28","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s12011-007-8051-1","article-title":"Leaching of\ntrace elements from biological tissue by formalin fixation","volume":"121","author":"Gellein","year":"2008","journal-title":"Biological Trace Element Research"},{"issue":"2","key":"2026073101214024700_cit29","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1177\/104063870802000213","article-title":"The effects\nof formalin fixation and tissue embedding of bovine liver on copper,\niron, and zinc analysis","volume":"20","author":"Bischoff","year":"2008","journal-title":"Journal of Veterinary\nDiagnostic Investigation"},{"key":"2026073101214024700_cit30","doi-asserted-by":"publisher","DOI":"10.1016\/j.sab.2020.105971","article-title":"Feasibility\nstudy of\nelemental analysis of large population of formalin fixed paraffin\nembedded tissue samples \u2013 preliminary results","volume":"173","author":"Wro\u0301bel","year":"2020","journal-title":"Spectrochim. Acta"},{"issue":"4","key":"2026073101214024700_cit31","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.jtemb.2008.03.010","article-title":"Analysis of iron,\nzinc, selenium and cadmium in paraffin-embedded\nprostate tissue specimens using inductively coupled plasma mass-spectrometry","volume":"22","author":"Sarafanov","year":"2008","journal-title":"Journal of Trace Elements in Medicine and Biology"},{"key":"2026073101214024700_cit32","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.placenta.2022.12.003","article-title":"Comparison of trace element concentrations\nin paired\nformalin-fixed paraffin-embedded and frozen human placentae","volume":"131","author":"Coyte","year":"2023","journal-title":"Placenta"},{"issue":"7","key":"2026073101214024700_cit33","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1007\/s00216-016-0124-6","article-title":"A comparison of sample\npreparation strategies for biological\ntissues and subsequent trace element analysis using LA-ICP-MS","volume":"409","author":"Bonta","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"issue":"5","key":"2026073101214024700_cit34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155132","article-title":"Clinicopathological\ncharacteristics of mucinous breast cancer: A retrospective analysis\nof a 10-year study","volume":"11","author":"Lei","year":"2016","journal-title":"PLoS One"},{"issue":"3","key":"2026073101214024700_cit35","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1111\/ggr.12161","article-title":"Nitrile, latex, neoprene and vinyl\ngloves: a primary source of contamination for trace element and zn\nisotopic analyses in geological and biological samples","volume":"41","author":"Garc\u0327on","year":"2017","journal-title":"Geostandards and Geoanalytical Research"},{"key":"2026073101214024700_cit36","volume-title":"HistoCore PELORIS 3 Premium\nTissue Processing System User\nManual","author":"Leica Biosystems.","year":"2020"},{"key":"2026073101214024700_cit37","volume-title":"Exploratory Data Analysis","author":"Tukey","year":"1977"},{"issue":"1","key":"2026073101214024700_cit38","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source\nsoftware for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"2026073101214024700_cit39","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1007\/978-3-030-00889-5_31","article-title":"Monte-Carlo sampling\napplied to multiple instance learning for histological image classification","volume-title":"Deep Learning in Medical Image Analysis and Multimodal\nLearning for Clinical Decision Support, Cham","author":"Combalia","year":"2018"},{"issue":"4","key":"2026073101214024700_cit40","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1214\/aos\/1176325770","article-title":"Large Sample Confidence Regions Based on Subsamples\nunder Minimal Assumptions","volume":"22","author":"Politis","year":"1994","journal-title":"Ann. Stat."},{"key":"2026073101214024700_cit41","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.aca.2018.05.019","article-title":"Assessment\nof discriminant models in infrared imaging using constrained repeated\nrandom sampling \u2013 Cross validation","volume":"1033","author":"Pe\u0301rez-Guaita","year":"2018","journal-title":"Anal.\nChim. Acta"},{"key":"2026073101214024700_cit42","doi-asserted-by":"publisher","DOI":"10.1016\/j.seppur.2021.119316","article-title":"Hydrodynamic\ncharacterisation of flotation impeller designs using Positron Emission\nParticle Tracking (PEPT)","volume":"276","author":"Mesa","year":"2021","journal-title":"Sep. Purif. Technol."},{"key":"2026073101214024700_cit43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2024.120673","article-title":"Mapping morphological\ncortical networks with joint probability distributions\nfrom multiple morphological features","volume":"296","author":"Wang","year":"2024","journal-title":"NeuroImage"},{"issue":"7","key":"2026073101214024700_cit44","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1109\/TIT.2003.813506","article-title":"A new metric\nfor probability distributions","volume":"49","author":"Endres","year":"2003","journal-title":"IEEE Transactions\non Information Theory"},{"issue":"3","key":"2026073101214024700_cit45","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/BF02517812","article-title":"A new class of metric\ndivergences on probability spaces and its applicability\nin statistics","volume":"55","author":"O\u0308sterreicher","year":"2003","journal-title":"Annals of the Institute of Statistical\nMathematics"},{"issue":"2","key":"2026073101214024700_cit46","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0016-0032(96)00063-4","article-title":"The Jensen-Shannon\ndivergence","volume":"334","author":"Mene\u0301ndez","year":"1997","journal-title":"Journal of the Franklin Institute"},{"issue":"1","key":"2026073101214024700_cit47","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1039\/C5JA00115C","article-title":"Improvements\nin Cd stable isotope analysis achieved through use of liquid\u2013liquid\nextraction to remove organic residues from Cd separates obtained by\nextraction chromatography","volume":"31","author":"Murphy","year":"2016","journal-title":"Journal of Analytical\nAtomic Spectrometry"},{"issue":"3","key":"2026073101214024700_cit48","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/0009-2541(95)00143-3","article-title":"Separation\nof Ce from other rare-earth elements with application to Sm Nd and\nLa Ce chronometry","volume":"129","author":"Rehka\u0308mper","year":"1996","journal-title":"Chem. Geol."},{"issue":"26","key":"2026073101214024700_cit49","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1242\/jcs.s3-94.26.125","article-title":"Cell\nshrinkage caused by fixatives and paraffin-wax embedding in ordinary\ncytological preparations","volume":"s3\u201394","author":"Ross","year":"1953","journal-title":"Journal of Cell Science"},{"issue":"8","key":"2026073101214024700_cit50","doi-asserted-by":"publisher","first-page":"759","DOI":"10.7150\/jca.12094","article-title":"Correcting\nthe Shrinkage\nEffects of Formalin Fixation and Tissue Processing for Renal Tumors:\ntoward Standardization of Pathological Reporting of Tumor Size","volume":"6","author":"Tran","year":"2015","journal-title":"J. Cancer"},{"issue":"12","key":"2026073101214024700_cit51","doi-asserted-by":"publisher","first-page":"2744","DOI":"10.1111\/ans.17109","article-title":"Skin tumour specimen shrinkage with excision and formalin fixation\u2500how\nmuch and why: a prospective study and discussion of the literature","volume":"91","author":"de Waal","year":"2021","journal-title":"Aust. N. Z. J. Surg."},{"issue":"13","key":"2026073101214024700_cit52","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1088\/0031-9155\/47\/13\/310","article-title":"Concentrations of Fe, Cu and Zn in\nbreast tissue: a synchrotron XRF study","volume":"47","author":"Geraki","year":"2002","journal-title":"Physics\nin Medicine & Biology"},{"key":"2026073101214024700_cit53","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/S0168-583X(03)01672-0","article-title":"A synchrotron\nXRF study on trace elements and potassium in breast tissue","volume":"213","author":"Geraki","year":"2004","journal-title":"Nucl. Instrum. Methods Phys. Res."},{"issue":"10","key":"2026073101214024700_cit54","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1016\/j.sab.2006.06.002","article-title":"Trace elements in human\ncancerous and healthy tissues from the same individual: A comparative\nstudy by TXRF and EDXRF","volume":"61","author":"Magalha\u0303es","year":"2006","journal-title":"Spectrochim. Acta"},{"key":"2026073101214024700_cit55","first-page":"404","article-title":"Significance of differential\nmetal loads in normal versus cancerous cadaver tissues","volume":"46","author":"Farah","year":"2010","journal-title":"Biomed Sci. Instrum"},{"key":"2026073101214024700_cit56","first-page":"63","article-title":"Metallothionein and\nmanganese concentrations in breast cancer and mastopathic tissues","volume":"5","author":"Florianczyk","year":"2011","journal-title":"J. Pre-Clin Clin Res."},{"issue":"6","key":"2026073101214024700_cit57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099790","article-title":"Serum and tissue zinc in epithelial\nmalignancies: A meta-analysis","volume":"9","author":"Gumulec","year":"2014","journal-title":"PLoS One"},{"issue":"5","key":"2026073101214024700_cit58","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1002\/1097-0142(19830901)52:5&lt;868::AID-CNCR2820520521&gt;3.0.CO;2-K","article-title":"Copper and\nzinc levels in normal\nand malignant tissues","volume":"52","author":"Margalioth","year":"1983","journal-title":"Cancer"},{"issue":"7","key":"2026073101214024700_cit59","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1007\/s00432-015-1932-3","article-title":"Zinc distribution\nwithin breast cancer tissue: A possible marker for histological grading?","volume":"141","author":"Riesop","year":"2015","journal-title":"Journal of Cancer Research and Clinical Oncology"},{"issue":"11","key":"2026073101214024700_cit60","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.1088\/0031-9155\/53\/11\/018","article-title":"The distribution of trace elements Ca, Fe, Cu and Zn\nand the determination of copper oxidation state in breast tumour tissue\nusing \u03bcSRXRF and \u03bcXANES","volume":"53","author":"Farquharson","year":"2008","journal-title":"Physics\nin Medicine & Biology"},{"issue":"3","key":"2026073101214024700_cit61","first-page":"3671","article-title":"The association between deficient manganese levels\nand breast cancer:\na meta-analysis","volume":"8","author":"Shen","year":"2015","journal-title":"Int. J. Clin Exp Med."},{"issue":"1","key":"2026073101214024700_cit62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054138","article-title":"Rapid two-temperature\nformalin fixation","volume":"8","author":"Chafin","year":"2013","journal-title":"PLoS One"},{"key":"2026073101214024700_cit63","unstructured":"RCPA Cancer Services Advisory Committee.\n          .  Fixation. 2019. https:\/\/www.rcpa.edu.au\/Manuals\/Macroscopic-Cut-Up-Manual\/General-information\/Fixation."},{"issue":"1","key":"2026073101214024700_cit64","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.stem.2008.05.018","article-title":"Transcriptome\nanalysis of the normal human mammary\ncell commitment and differentiation process","volume":"3","author":"Raouf","year":"2008","journal-title":"Cell Stem Cell"},{"issue":"5","key":"2026073101214024700_cit65","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"issue":"3","key":"2026073101214024700_cit66","doi-asserted-by":"publisher","first-page":"111","DOI":"10.4102\/jsava.v73i3.570","article-title":"The effect\nof storage conditions\non samples for the evaluation of copper status in blesbok (Damaliscus\npygargus phillipsi)","volume":"73","author":"Quan","year":"2002","journal-title":"Journal of the South African\nVeterinary Association"},{"key":"2026073101214024700_cit67","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2024.110281","article-title":"The impact of formalin\nfixation in the elemental content of tissues: Parametrization up to\n48 h","volume":"200","author":"Silva","year":"2024","journal-title":"Microchemical Journal"},{"issue":"3","key":"2026073101214024700_cit68","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1039\/C3JA50281C","article-title":"The\neffect of paraformaldehyde\nfixation and sucrose cryoprotection on metal concentration in murine\nneurological tissue","volume":"29","author":"Hare","year":"2014","journal-title":"Journal of Analytical Atomic\nSpectrometry"},{"issue":"5","key":"2026073101214024700_cit69","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/labinvest.2015.37","article-title":"Critical roles\nof specimen type and temperature before and during fixation in the\ndetection of phosphoproteins in breast cancer tissues","volume":"95","author":"Gu\u0308ndisch","year":"2015","journal-title":"Laboratory Investigation"},{"issue":"8","key":"2026073101214024700_cit70","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1177\/33.8.3894502","article-title":"Formaldehyde fixation","volume":"33","author":"Fox","year":"1985","journal-title":"Journal\nof Histochemistry & Cytochemistry"},{"issue":"16","key":"2026073101214024700_cit71","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1200\/JCO.2009.25.6529","article-title":"American\nSociety of Clinical Oncology\/College of American\nPathologists Guideline recommendations for immunohistochemical testing\nof estrogen and progesterone receptors in breast cancer","volume":"28","author":"Hammond","year":"2010","journal-title":"Journal of Clinical Oncology"},{"key":"2026073101214024700_cit72","volume-title":"Guidelines Working Group of the UK National Coordinating\nCommittee\nfor Breast Pathology: Dataset for histopathological reporting of breast\ndisease in surgical excision specimens of breast cancer","year":"2024"}],"container-title":["Chemical &amp; Biomedical\nImaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/cbmi.5c00217","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article-pdf\/4\/7\/1390\/66282304\/cbmi.5c00217.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article-pdf\/4\/7\/1390\/66282304\/cbmi.5c00217.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:21:51Z","timestamp":1785475311000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/cbihbp\/article\/4\/7\/1390\/5234120\/Impact-of-Histological-Processing-on-Endogenous"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":72,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,2,4]]},"published-print":{"date-parts":[[2026,7,27]]}},"URL":"https:\/\/doi.org\/10.1021\/cbmi.5c00217","relation":{},"ISSN":["2832-3637"],"issn-type":[{"value":"2832-3637","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]}}}