{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:17:06Z","timestamp":1790705826543,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P2SKP3_168322\/2"],"award-info":[{"award-number":["P2SKP3_168322\/2"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P30325\u2010B28"],"award-info":[{"award-number":["P30325\u2010B28"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006069","name":"Krebsliga Beider Basel","doi-asserted-by":"publisher","award":["KLbB\u20104182\u201003\u20102017"],"award-info":[{"award-number":["KLbB\u20104182\u201003\u20102017"]}],"id":[{"id":"10.13039\/501100006069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardised digital protocol for the assessment of\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      In two cohorts with a total of 69 cutaneous melanomas, a highly significant correlation was found between pathologist\u2010based consensus reading and automated\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 analysis (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.97,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). Digital scoring captured the full diagnostic spectrum of\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 expression at single cell resolution. An average of 150\u00a0472 melanoma cells (median 38\u00a0668 cells; range\u00a0=\u00a0733\u20131\u00a0078\u00a0965) were scored per lesion. Machine learning was used to control for heterogeneity introduced by\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1\u2010positive inflammatory cells in the tumour microenvironment. The\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 image analysis protocol showed excellent reproducibility (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a01.0,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) when carried out on independent workstations and reduced variability in\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 scoring of human observers. When melanomas were grouped by\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 expression status, we found a clear correlation of\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 positivity with\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      8\u2010positive T cell infiltration, but not with tumour stage, metastasis or driver mutation status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Digital evaluation of\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010L1 reduces scoring variability and may facilitate patient stratification in clinical practice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.13528","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T12:16:19Z","timestamp":1523880979000},"page":"397-406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Digital image analysis improves precision of\n                    <scp>PD<\/scp>\n                    \u2010L1 scoring in cutaneous melanoma"],"prefix":"10.1111","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9206-4885","authenticated-orcid":false,"given":"Viktor H","family":"Koelzer","sequence":"first","affiliation":[{"name":"Cantonal Hospital Baselland Institute of Pathology Liestal Switzerland"},{"name":"Translational Research Unit (TRU) Institute of Pathology University of Bern Bern 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