{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:34:11Z","timestamp":1790771651691,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004327","name":"SingHealth Foundation","doi-asserted-by":"publisher","award":["SHF\/FG668S\/2015"],"award-info":[{"award-number":["SHF\/FG668S\/2015"]}],"id":[{"id":"10.13039\/501100004327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate tertiary lymphoid structures (TLSs) in ductal carcinoma <jats:italic>in\u00a0situ<\/jats:italic> (DCIS) of the breast and their correlation with pathological features, immune cell markers and clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Morphological identification of TLSs in 198 DCIS cases incorporated B and T cell zones with high endothelial venules. TLS positivity was defined as \u2265\u20091 TLSs in lesional areas, while TLS area percentage was divided into two categories: low (TLSs &lt;\u20095%) and high (TLSs \u2265\u20095%). Previously reported biomarkers included ER, PR, HER2, CD68, CD163, CD4, CD8 and PD\u2010L1. TLSs were observed in 24.7% (49 of 198) of cases, with a mean diameter of 0.44\u2009mm (median\u00a0=\u00a00.4\u2009mm, range\u00a0=\u00a00.12\u20131.43\u2009mm). TLSs were significantly associated with higher nuclear grade, presence of necrosis, hormone receptor negativity\/HER2 positivity, triple negativity, tumour infiltrating lymphocytes (TILs) and immune related biomarkers such as FOXP3, CD163, CD4 and CD4\/CD8 ratio (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.05). There were no significant associations between TLSs and recurrence, but a combination of TLSs<jats:sup>high<\/jats:sup> with FOXP3<jats:sup>+<\/jats:sup>, CD4<jats:sup>high<\/jats:sup>, CD4\/CD8 ratio<jats:sup>high<\/jats:sup> and CD68<jats:sup>high<\/jats:sup> individually, compared with all other combinations, disclosed significantly poorer disease\u2010free survival (DFS) for ipsilateral invasive recurrence (IIR) on both Kaplan\u2013Meier and multivariable Cox regression analyses (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TLSs in DCIS were associated with unfavourable prognostic features, TILs and immune cell markers in our study. TLSs<jats:sup>high<\/jats:sup>\/FoxP3<jats:sup>+<\/jats:sup>, TLSs<jats:sup>high<\/jats:sup>\/CD4<jats:sup>high<\/jats:sup>, TLSs<jats:sup>high<\/jats:sup>\/(CD4\/CD8) ratio<jats:sup>high<\/jats:sup> and TLSs<jats:sup>high<\/jats:sup>\/CD68<jats:sup>high<\/jats:sup> were independent factors for poorer DFS for IIR. Further exploration of the pathological significance of TLSs may provide a clinical basis for their recognition as an important structure and functional unit in the tumour immune microenvironment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14865","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T06:25:30Z","timestamp":1673591130000},"page":"779-788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tertiary lymphoid structures in breast ductal carcinoma <i>in\u00a0situ<\/i> correlate with adverse pathological parameters"],"prefix":"10.1111","volume":"82","author":[{"given":"Lixia","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Anatomical Pathology Singapore General Hospital  Singapore Singapore"},{"name":"Department of Pathology Guangxi Medical University Cancer Hospital  Nanning Guangxi 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