{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T02:47:30Z","timestamp":1770691650045,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T00:00:00Z","timestamp":1660348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA194600"],"award-info":[{"award-number":["R01CA194600"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-described race was genetically confirmed using QC Infinium array combined with radmixture software. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&amp;E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. In univariate survival analysis, age older than 50 years, hormone receptor positivity and the presence of circumferential TILs were weakly associated with the absence of BCE at the 5-year follow-up in all cohorts (p &lt; 0.03; p &lt; 0.02; and p &lt; 0.02, respectively, adjusted p = 0.11). In the multivariable analysis, circumferential TILs were an independent predictor of a better outcome (Wald test p = 0.01), whereas younger age was associated with BCE. Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone and may be added in guidelines for TILs evaluation in DCIS.<\/jats:p>","DOI":"10.3390\/cancers14163916","type":"journal-article","created":{"date-parts":[[2022,8,14]],"date-time":"2022-08-14T21:09:06Z","timestamp":1660511346000},"page":"3916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-9980","authenticated-orcid":false,"given":"Sunil S.","family":"Badve","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Winship Cancer Institute, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6715-9348","authenticated-orcid":false,"given":"Sanghee","family":"Cho","sequence":"additional","affiliation":[{"name":"GE Global Research Center, Niskayuna, NY 12309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics, Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sha","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics, Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya","family":"Ghose","sequence":"additional","affiliation":[{"name":"GE Global Research Center, Niskayuna, NY 12309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aye Aye","family":"Thike","sequence":"additional","affiliation":[{"name":"Anatomical Pathology, Singapore General Hospital, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puay Hoon","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Pathology, Singapore General Hospital, Singapore 169856, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idris Tolgay","family":"Ocal","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6002-1530","authenticated-orcid":false,"given":"Daniele","family":"Generali","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Zanconati","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-8409","authenticated-orcid":false,"given":"Adrian L.","family":"Harris","sequence":"additional","affiliation":[{"name":"Cancer and Haematology Centre, Department of Oncology, Oxford University, Oxford OX3 7LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Ginty","sequence":"additional","affiliation":[{"name":"GE Global Research Center, Niskayuna, NY 12309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9927-4893","authenticated-orcid":false,"given":"Yesim","family":"G\u00f6kmen-Polar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Winship Cancer Institute, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/annonc\/mdu450","article-title":"The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014","volume":"26","author":"Salgado","year":"2015","journal-title":"Ann. 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