{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T19:51:56Z","timestamp":1771962716242,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA 194600"],"award-info":[{"award-number":["R01CA 194600"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Tumour\u2010infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer; however, their prognostic significance in ductal carcinoma <jats:italic>in situ<\/jats:italic> (DCIS) has not been established. The Oncotype DX (ODX) Breast DCIS Score test is a genomic assay used to predict the local recurrence risk. The aims of this study were to quantify TILs in DCIS by the use of three methodologies, and correlate them with the ODX DCIS Score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We studied 97 DCIS cases, all with an ODX DCIS Score. Cases with a low ODX DCIS Score were considered as one group, and those with an intermediate\/high ODX Score were considered together. TILs were quantified on haematoxylin and eosin\u2010stained slides. The methodologies used to quantify TILS included assessment of stromal TILs, assessment of touching TILs, and assessment of circumferential TILS. In cases with &gt;5% stromal TILS, the percentage of stromal TILS was considered to be high. In cases with a mean number of more than five touching TILs per DCIS duct, TILs were considered to be present. The ODX DCIS Score was intermediate\/high in 27 (28%) cases and low in 70 (72%) cases. There were &gt;5% stromal TILs in 33 (34%) cases, and more than five touching TILs per DCIS duct in 15 (15%) cases; circumferential TILs were present in nine (9%) cases. In univariate analysis, a low ODX DCIS Score showed significant associations with absent touching TILS (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.027), stromal TILs\u00a0&lt;\u00a05% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.031), and absent circumferential TILs (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002). In logistic regression analysis adjusted for necrosis and nuclear grade, touching TILs and circumferential TILs showed significant associations with the ODX DCIS Score, whereas stromal TILs did not.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that both the presence of TILs and the spatial arrangement of TILs or close proximity of TILs to DCIS, and TILs touching or encircling DCIS, may be predictive of recurrence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14181","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T21:09:49Z","timestamp":1592428189000},"page":"749-759","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Tumour\u2010infiltrating lymphocytes in ductal carcinoma <i>in situ<\/i> (DCIS)\u2014assessment with three different methodologies and correlation with Oncotype DX DCIS Score"],"prefix":"10.1111","volume":"77","author":[{"given":"Miglena","family":"Komforti","sequence":"first","affiliation":[{"name":"Department of Pathology Montefiore Medical Center Albert Einstein College of Medicine  Bronx NY USA"},{"name":"Department of Pathology Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil S","family":"Badve","sequence":"additional","affiliation":[{"name":"Department of Pathology Indiana University  Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan","family":"Harmon","sequence":"additional","affiliation":[{"name":"Department of Pathology Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yungtai","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-7875","authenticated-orcid":false,"given":"Susan","family":"Fineberg","sequence":"additional","affiliation":[{"name":"Department of Pathology Montefiore Medical Center Albert Einstein College of Medicine  Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djr027"},{"key":"e_1_2_8_4_1","first-page":"162","article-title":"Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast","volume":"41","author":"Correa C","year":"2010","journal-title":"J. Natl Cancer Inst. Monogr."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.1100"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.9029"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","unstructured":"McCormickB.Randomized trial evaluating radiation following surgical excision for \u2018good risk\u2019 DCIS: 12\u2010year report from 415NRG\/RTOG 9804. 2018 ASTRO Annual Meeting. Abstract no. 416LBA1.","DOI":"10.1016\/j.ijrobp.2018.08.048"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt067"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-015-3464-6"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1002\/jso.23933","article-title":"The impact of the genomic testing on the recommendation for radiation therapy in patients with ductal carcinoma in situ: a prospective clinical utility assessment of the 12\u2010gene DCIS Score result","volume":"111","author":"Alvardo M","year":"2015","journal-title":"J. Surg. Oncol."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-016-0165-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152500"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-019-07562-x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw623"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0040-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0030-x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.semcancer.2017.10.003","article-title":"Update on tumor\u2010infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILS in residual disease after neoadjuvant therapy and in carcinoma in situ: a report of the International Immuno\u2010Oncology Biomarker Working Group on Breast Cancer","volume":"52","author":"Vittorio Dieci M","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/modpathol.2015.79","article-title":"Correlation of the histopathologic features of ductal carcinoma in situ of the breast with the oncotype DX DCIS Score","volume":"18","author":"Knopfelmacher A","year":"2015","journal-title":"Mod. Pathol."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0743"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.172"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1111\/his.14055","article-title":"Higher densities of tumor\u2010infiltrating lymphocytes and CD4+ T cells predict recurrence and progression of ductal carcinoma in situ of the breast","volume":"75","author":"Thike A","year":"2020","journal-title":"Histopathology"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13217"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.cell.2018.08.039","article-title":"A structured tumor\u2010immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging","volume":"17","author":"Keren L","year":"2018","journal-title":"Cell"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1218106"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.158"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0331-8"},{"key":"e_1_2_8_27_1","first-page":"1432","article-title":"Higher density of stromal M2 macrophages in breast ductal carcinoma in situ predicts recurrence","volume":"476","author":"Xiao\u2010Yang C","year":"2020","journal-title":"Virchows Arch."},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0797-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cam4.715","article-title":"CD8+ tumor\u2010infiltrating lymphocytes contribute to spontaneous healing in HER2\u2010positive ductal carcinoma in situ","volume":"5","author":"Morita M","year":"2016","journal-title":"Cancer Med."},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-4013-6"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.2.232"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.14181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.14181","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T02:52:35Z","timestamp":1693882355000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.14181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,26]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/his.14181"],"URL":"https:\/\/doi.org\/10.1111\/his.14181","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,26]]},"assertion":[{"value":"2020-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}