{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:09:29Z","timestamp":1790834969090,"version":"4.1.0"},"reference-count":47,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["2011-5152"],"award-info":[{"award-number":["2011-5152"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["2017-10978"],"award-info":[{"award-number":["2017-10978"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["mp.uscap.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Modern Pathology"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.modpat.2023.100199","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T20:53:21Z","timestamp":1682542401000},"page":"100199","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["Using Intratumor Heterogeneity of Immunohistochemistry Biomarkers to Classify Laryngeal and Hypopharyngeal Tumors Based on Histologic Features"],"prefix":"10.1016","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7212-2694","authenticated-orcid":false,"given":"Hilde J.G.","family":"Smits","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian N.","family":"Ruiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben E.","family":"Breimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle E.P.","family":"Philippens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.modpat.2023.100199_bib1","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1158\/1078-0432.CCR-14-1429","article-title":"Translational implications of tumor heterogeneity","volume":"21","author":"Jamal-Hanjani","year":"2015","journal-title":"Clin Cancer Res"},{"issue":"2","key":"10.1016\/j.modpat.2023.100199_bib2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00109-020-01874-2","article-title":"Clinical implications of intratumor heterogeneity: challenges and opportunities","volume":"98","author":"Ram\u00f3n","year":"2020","journal-title":"J\u00a0Mol Med (Berl)"},{"issue":"4","key":"10.1016\/j.modpat.2023.100199_bib3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccell.2020.03.007","article-title":"Intratumor heterogeneity: the Rosetta Stone of therapy resistance","volume":"37","author":"Marusyk","year":"2020","journal-title":"Cancer Cell"},{"issue":"2","key":"10.1016\/j.modpat.2023.100199_bib4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.wjorl.2016.05.007","article-title":"Intra-tumor heterogeneity in head and neck cancer and its clinical implications","volume":"2","author":"Mroz","year":"2016","journal-title":"World J Otorhinolaryngol Head Neck Surg"},{"issue":"4","key":"10.1016\/j.modpat.2023.100199_bib5","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.cell.2013.01.019","article-title":"Evolution and impact of subclonal mutations in chronic lymphocytic leukemia","volume":"152","author":"Landau","year":"2013","journal-title":"Cell"},{"issue":"6206","key":"10.1016\/j.modpat.2023.100199_bib6","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.1256930","article-title":"Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing","volume":"346","author":"Zhang","year":"2014","journal-title":"Science"},{"issue":"22","key":"10.1016\/j.modpat.2023.100199_bib7","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1056\/NEJMoa1616288","article-title":"Tracking the evolution of non\u2013small-cell lung cancer","volume":"376","author":"Jamal-Hanjani","year":"2017","journal-title":"N\u00a0Engl J Med"},{"issue":"1","key":"10.1016\/j.modpat.2023.100199_bib8","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"issue":"7","key":"10.1016\/j.modpat.2023.100199_bib9","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat Methods"},{"issue":"7","key":"10.1016\/j.modpat.2023.100199_bib10","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological image analysis","volume":"9","author":"Schindelin","year":"2009","journal-title":"Nat Methods"},{"issue":"7","key":"10.1016\/j.modpat.2023.100199_bib11","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nmeth.2075","article-title":"Icy: an open bioimage informatics platform for extended reproducible research","volume":"9","author":"De Chaumont","year":"2012","journal-title":"Nat Methods"},{"issue":"1","key":"10.1016\/j.modpat.2023.100199_bib12","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2144\/000112257","article-title":"CellProfiler: free, versatile software for automated biological image analysis","volume":"42","author":"Lamprecht","year":"2007","journal-title":"Biotechniques"},{"issue":"6","key":"10.1016\/j.modpat.2023.100199_bib13","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1109\/TSMC.1973.4309314","article-title":"Textural features for image classification","volume":"SMC-3","author":"Haralick","year":"1973","journal-title":"IEEE Trans Syst Man Cybern"},{"issue":"2","key":"10.1016\/j.modpat.2023.100199_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0212110","article-title":"Gray-level invariant Haralick texture features","volume":"14","author":"L\u00f6fstedt","year":"2019","journal-title":"PLoS One"},{"issue":"3","key":"10.1016\/j.modpat.2023.100199_bib15","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/mrm.21347","article-title":"Volumetric texture analysis of breast lesions on contrast-enhanced magnetic resonance images","volume":"58","author":"Chen","year":"2007","journal-title":"Magn Reson Med"},{"issue":"7","key":"10.1016\/j.modpat.2023.100199_bib16","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1088\/0031-9155\/60\/7\/2685","article-title":"Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness","volume":"60","author":"Vignati","year":"2015","journal-title":"Phys Med Biol"},{"issue":"9","key":"10.1016\/j.modpat.2023.100199_bib17","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0108335","article-title":"Glioma: application of whole-tumor texture analysis of diffusion-weighted imaging for the evaluation of tumor heterogeneity","volume":"9","author":"Ryu","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.modpat.2023.100199_bib18","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jmri.25335","article-title":"Haralick textural features on T2-weighted MRI are associated with biochemical recurrence following radiotherapy for peripheral zone prostate cancer","volume":"45","author":"Gnep","year":"2017","journal-title":"J\u00a0Magn Reson Imaging"},{"key":"10.1016\/j.modpat.2023.100199_bib19","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2020.599050","article-title":"Hormonal receptor immunochemistry heterogeneity and 18F-FDG metabolic heterogeneity: preliminary results of their relationship and prognostic value in luminal non-metastatic breast cancers","volume":"10","author":"Aide","year":"2021","journal-title":"Front Oncol"},{"key":"10.1016\/j.modpat.2023.100199_bib20","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.774088","article-title":"Intratumoral heterogeneity and immune response indicators to predict overall survival in a retrospective study of HER2-borderline (IHC 2+) breast cancer patients","volume":"11","author":"Radziuviene","year":"2021","journal-title":"Front Oncol"},{"issue":"12","key":"10.1016\/j.modpat.2023.100199_bib21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/cancers12123663","article-title":"Identifying cross-scale associations between radiomic and pathomic signatures of non-small cell lung cancer subtypes: preliminary results","volume":"12","author":"Alvarez-Jimenez","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"6","key":"10.1016\/j.modpat.2023.100199_bib22","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S1808-8694(15)30145-2","article-title":"Prognostic value of the immunohistochemistry correlation of Ki-67 and p53 in squamous cell carcinomas of the larynx","volume":"74","author":"Rodrigues","year":"2008","journal-title":"Braz J Otorhinolaryngol"},{"issue":"4","key":"10.1016\/j.modpat.2023.100199_bib23","doi-asserted-by":"crossref","first-page":"661","DOI":"10.4103\/0377-4929.72019","article-title":"Expression of Ki67 and P53 in primary squamous cell carcinoma of the larynx","volume":"53","author":"Ashraf","year":"2010","journal-title":"Indian J Pathol Microbiol"},{"issue":"6","key":"10.1016\/j.modpat.2023.100199_bib24","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1097\/00005537-200006000-00024","article-title":"Ki-67 (MIB1), p53, and Lewis-X (LeuM1) as prognostic factors of recurrence in T1 and T2 laryngeal carcinoma","volume":"110","author":"Sittel","year":"2000","journal-title":"Laryngoscope"},{"issue":"2","key":"10.1016\/j.modpat.2023.100199_bib25","first-page":"107","article-title":"Expression of leukocyte common antigen (CD45) on various human leukemia\/lymphoma cell lines","volume":"40","author":"Nakano","year":"1990","journal-title":"Acta Pathol Jpn"},{"issue":"1","key":"10.1016\/j.modpat.2023.100199_bib26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00405-017-4806-2","article-title":"Prognostic value of CD45 transcriptional expression in head and neck cancer","volume":"275","author":"Camacho","year":"2018","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"3","key":"10.1016\/j.modpat.2023.100199_bib27","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/hed.23736","article-title":"Clinical relevance of immune parameters in the tumor microenvironment of head and neck cancers","volume":"37","author":"Wallis","year":"2015","journal-title":"Head Neck"},{"issue":"12","key":"10.1016\/j.modpat.2023.100199_bib28","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1038\/s41379-022-01137-0","article-title":"Intratumoral spatial heterogeneity of tumor-infiltrating lymphocytes is a significant factor for precisely stratifying prognostic immune subgroups of microsatellite instability-high colorectal carcinomas","volume":"35","author":"Jung","year":"2022","journal-title":"Mod Pathol"},{"issue":"2","key":"10.1016\/j.modpat.2023.100199_bib29","doi-asserted-by":"crossref","first-page":"e289","DOI":"10.1016\/j.ijrobp.2011.05.004","article-title":"Validation of imaging with pathology in laryngeal cancer: accuracy of the registration methodology","volume":"82","author":"Caldas-Magalhaes","year":"2012","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"11","key":"10.1016\/j.modpat.2023.100199_bib30","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1080\/0284186X.2016.1219048","article-title":"Validated guidelines for tumor delineation on magnetic resonance imaging for laryngeal and hypopharyngeal cancer","volume":"55","author":"Jager","year":"2016","journal-title":"Acta Oncol"},{"key":"10.1016\/j.modpat.2023.100199_bib31","series-title":"Carcinomas of the Hypopharynx, Larynx and Trachea Histopathology Reporting Guide","author":"Helliwell","year":"2018"},{"issue":"4","key":"10.1016\/j.modpat.2023.100199_bib32","first-page":"291","article-title":"Quantification of histochemical staining by color deconvolution","volume":"23","author":"Ruifrok","year":"2001","journal-title":"Anal Quant Cytol Histol"},{"key":"10.1016\/j.modpat.2023.100199_bib33","series-title":"Fast Calculation of Haralick Features. Tech Report","author":"Miyamoto","year":"2008"},{"issue":"4","key":"10.1016\/j.modpat.2023.100199_bib34","first-page":"193","article-title":"The representations of sonographic image texture for breast cancer using co-occurrence matrix","volume":"25","author":"Chen","year":"2005","journal-title":"J\u00a0Med Biol Eng"},{"issue":"3","key":"10.1016\/j.modpat.2023.100199_bib35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.oraloncology.2012.09.007","article-title":"MATH, a novel measure of intratumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma","volume":"49","author":"Mroz","year":"2013","journal-title":"Oral Oncol"},{"issue":"16","key":"10.1016\/j.modpat.2023.100199_bib36","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1002\/cncr.28150","article-title":"High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma","volume":"119","author":"Mroz","year":"2013","journal-title":"Cancer"},{"key":"10.1016\/j.modpat.2023.100199_bib37","doi-asserted-by":"crossref","DOI":"10.1038\/srep37767","article-title":"Measuring intratumor heterogeneity by network entropy using RNA-seq data","volume":"6","author":"Park","year":"2016","journal-title":"Sci Rep"},{"issue":"11","key":"10.1016\/j.modpat.2023.100199_bib38","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2017.1356148","article-title":"The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis","volume":"6","author":"de Ruiter","year":"2017","journal-title":"Oncoimmunology"},{"issue":"6","key":"10.1016\/j.modpat.2023.100199_bib39","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.3390\/cancers14061558","article-title":"Tumor-infiltrating lymphocytes in head and neck cancer: ready for prime time?","volume":"14","author":"Almangush","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"3","key":"10.1016\/j.modpat.2023.100199_bib40","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/his.12754","article-title":"Reproducibility and prognostic value of pattern of invasion scoring in low-stage oral squamous cell carcinoma","volume":"68","author":"Heerema","year":"2016","journal-title":"Histopathology"},{"issue":"1","key":"10.1016\/j.modpat.2023.100199_bib41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1034\/j.1600-0714.2003.00060.x","article-title":"Invasive front grading: reliability and usefulness in the management of oral squamous cell carcinoma","volume":"32","author":"Sawair","year":"2003","journal-title":"J\u00a0Oral Pathol Med"},{"issue":"4-5","key":"10.1016\/j.modpat.2023.100199_bib42","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.oraloncology.2008.07.016","article-title":"Pitfalls and procedures in the histopathological diagnosis of oral and oropharyngeal squamous cell carcinoma and a review of the role of pathology in prognosis","volume":"45","author":"Woolgar","year":"2009","journal-title":"Oral Oncol"},{"issue":"1","key":"10.1016\/j.modpat.2023.100199_bib43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00428-022-03326-3","article-title":"Detection of perineural invasion in prostate needle biopsies with deep neural networks","volume":"481","author":"Kartasalo","year":"2022","journal-title":"Virchows Arch"},{"issue":"4","key":"10.1016\/j.modpat.2023.100199_bib44","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/cac2.12012","article-title":"Emerging role of deep learning-based artificial intelligence in tumor pathology","volume":"40","author":"Jiang","year":"2020","journal-title":"Cancer Commun (Lond)"},{"key":"10.1016\/j.modpat.2023.100199_bib45","series-title":"Incorporating intratumoral heterogeneity into weakly-supervised deep learning models via variance pooling. International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI)","first-page":"387","author":"Carmichael","year":"2022"},{"key":"10.1016\/j.modpat.2023.100199_bib46","doi-asserted-by":"crossref","DOI":"10.1038\/srep42964","article-title":"Image processing in digital pathology : an opportunity to solve inter-batch variability of immunohistochemical staining","volume":"7","author":"Van Eycke","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"10.1016\/j.modpat.2023.100199_bib47","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1038\/s41598-017-04151-4","article-title":"Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters","volume":"7","author":"Brynolfsson","year":"2017","journal-title":"Sci Rep"}],"container-title":["Modern Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0893395223001047?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0893395223001047?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:24:00Z","timestamp":1760232240000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0893395223001047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["S0893395223001047"],"URL":"https:\/\/doi.org\/10.1016\/j.modpat.2023.100199","relation":{},"ISSN":["0893-3952"],"issn-type":[{"value":"0893-3952","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Using Intratumor Heterogeneity of Immunohistochemistry Biomarkers to Classify Laryngeal and Hypopharyngeal Tumors Based on Histologic Features","name":"articletitle","label":"Article Title"},{"value":"Modern Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.modpat.2023.100199","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology.","name":"copyright","label":"Copyright"}],"article-number":"100199"}}