{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:30:40Z","timestamp":1777663840444,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["2022A019104"],"award-info":[{"award-number":["2022A019104"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA240317"],"award-info":[{"award-number":["R01 CA240317"]}],"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":[[2023,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Small cell lung carcinoma (SCLC) can be classified into transcription factor\u2010based subtypes (ASCL1, NeuroD1, POU2F3). While <jats:italic>in\u2010vitro<\/jats:italic> studies suggest intratumoral heterogeneity in the expression of these markers, how SCLC subtypes vary over time and among locations in patients remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We searched a consecutive series of patients at our institution in 2006\u201322 for those with greater than one available formalin\u2010fixed paraffin\u2010embedded SCLC sample in multiple sites and\/or time\u2010points. Immunohistochemistry for ASCL1, NeuroD1 and POU2F3 was performed and evaluated using H\u2010scores, with subtype assigned based on the positive marker (H\u2010score threshold &gt;10) with the highest H\u2010score. The 179 samples (75, lung; 51, lymph nodes; 53, non\u2010nodal metastases) from 84 patients (74 with two, 10 with more than two samples) included 98 (54.7%) ASCL1\u2010dominant, 47 (26.3%) NeuroD1\u2010dominant, 15 (8.4%) POU2F3\u2010dominant, 17 (9.5%) triple\u2010negative and two (1.1%) ASCL1\/NeuroD1 co\u2010dominant samples. NeuroD1\u2010dominant subtype was enriched in non\u2010lung locations. Subtype concordance from pairwise comparison was 71.4% overall and 89.7% after accounting for ASCL1\/NeuroD1\u2010dual expressors and technical factors including &lt;500 cells\/slide, H\u2010score thresholds and sample decalcification. No significant difference in subtype concordance was noted with a longer time lapse or with extrathoracic versus intrathoracic samples in this cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>After accounting for technical factors, transcription factor\u2010based subtyping was discordant among multiple SCLC samples in ~10% of patients, regardless of sample locations and time lapse. Our findings highlighted the spatiotemporal heterogeneity of SCLC in clinical samples and potential challenges, including technical and biological factors, that might limit concordance in SCLC transcription factor\u2010based subtyping.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15034","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T04:02:16Z","timestamp":1693368136000},"page":"912-924","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Concordance of ASCL1, NEUROD1 and POU2F3 transcription factor\u2010based subtype assignment in paired tumour samples from small cell lung carcinoma"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-7691","authenticated-orcid":false,"given":"Thomas","family":"Denize","sequence":"first","affiliation":[{"name":"Department of Pathology Harvard Medical School, Massachusetts General Hospital  Boston MA 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