{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:03:59Z","timestamp":1740107039259,"version":"3.37.3"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum der Ruhr-Universit\u00e4t Bochum"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To investigate the protein expression of DNA mismatch repair (MMR) proteins in patients with cutaneous melanoma (CM) under immune checkpoint inhibitor (ICI) therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Immunohistochemistry was performed on tumor tissue for MMR proteins MLH1, MSH2, MSH6, and PMS2 in 50 metastatic CM patients treated with ICI (ipilimumab, nivolumab, pembrolizumab).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Best overall response (BOR) rate was 48% (24\/50). Reduced MMR protein expression (nuclear expression in\u2009&lt;\u200980% of tumor cells) was observed in 8 patients (16%). Compared to other clinical parameters, baseline neutrophil\/lymphocyte ratio and reduced intratumoral MMR protein expression (<jats:italic>P<\/jats:italic>\u2009=\u20090.0033) were determined as the only parameters significantly associated with favorable BOR. However, in this small study population, reduced MMR protein expression did not reach statistical significance in multivariate analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Reduced MMR protein expression is observed in CM and might predict favorable BOR in patients treated with ICI, as was observed for other entities. However, these findings need to be substantiated in larger patient cohorts.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-022-04002-4","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T18:03:03Z","timestamp":1649872983000},"page":"1241-1247","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression of DNA mismatch repair proteins in melanoma patients treated with immune checkpoint inhibitors"],"prefix":"10.1007","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-3695","authenticated-orcid":false,"given":"T.","family":"Gambichler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Finis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Abu Rached","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. H.","family":"Scheel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. C.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. U.","family":"K\u00e4fferlein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Br\u00fcning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Abolmaali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Susok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"4002_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1309\/ajcpcx2d9yulbblg","volume":"142","author":"E Alvino","year":"2014","unstructured":"Alvino E, Passarelli F, Cannav\u00f2 E, Fortes C, Mastroeni S, Caporali S, Jiricny J, Cappellini GCA, Scoppola A, Marchetti P et al (2014) High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma. Am J Clin Pathol 142:121\u2013132. https:\/\/doi.org\/10.1309\/ajcpcx2d9yulbblg","journal-title":"Am J Clin Pathol"},{"issue":"11","key":"4002_CR2","doi-asserted-by":"publisher","first-page":"639085","DOI":"10.3389\/fonc.2021.639085","volume":"20","author":"X Bai","year":"2021","unstructured":"Bai X, Dai J, Li C et al (2021) Risk models for advanced melanoma patients under anti-PD-1 monotherapy-Ad hoc Analyses of Pooled Data From Two Clinical Trials. Front Oncol 20(11):639085","journal-title":"Front Oncol"},{"key":"4002_CR3","doi-asserted-by":"publisher","first-page":"12","DOI":"10.21037\/tgh.2020.03.08","volume":"6","author":"R Breakstone","year":"2021","unstructured":"Breakstone R (2021) Colon cancer and immunotherapy-can we go beyond microsatellite instability? Transl Gastroenterol Hepatol 6:12. https:\/\/doi.org\/10.21037\/tgh.2020.03.08","journal-title":"Transl Gastroenterol Hepatol"},{"key":"4002_CR4","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.3389\/fimmu.2018.01474","volume":"9","author":"K Buder-Bakhaya","year":"2018","unstructured":"Buder-Bakhaya K, Hassel JC (2018) Biomarkers for clinical benefit of immune checkpoint inhibitor treatment-a review from the melanoma perspective and beyond. Front Immunol 9:1474","journal-title":"Front Immunol"},{"issue":"18","key":"4002_CR5","doi-asserted-by":"publisher","first-page":"4659","DOI":"10.3390\/cancers13184659","volume":"13","author":"YA Cho","year":"2021","unstructured":"Cho YA, Lee H, Kim DG, Kim H, Ha SY, Choi YL, Jang KT, Kim KM (2021) PD-L1 Expression Is significantly associated with tumor mutation burden and microsatellite instability Score. Cancers 13(18):4659","journal-title":"Cancers"},{"key":"4002_CR6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228\u2013247","journal-title":"Eur J Cancer"},{"issue":"5","key":"4002_CR7","doi-asserted-by":"publisher","first-page":"3316","DOI":"10.3390\/curroncol28050287","volume":"28","author":"T Gambichler","year":"2021","unstructured":"Gambichler T, Ganjuur N, Tannapfel A, Vogt M, Scholl L, Abu Rached N, Bruckm\u00fcller S, Skrygan M, Becker JC, K\u00e4fferlein HU, Br\u00fcning T, Lang K (2021a) Mismatch repair protein expression and microsatellite instability in cutaneous squamous cell carcinoma. Curr Oncol 28(5):3316\u20133322","journal-title":"Curr Oncol"},{"issue":"11","key":"4002_CR8","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.3390\/cancers13112524","volume":"13","author":"T Gambichler","year":"2021","unstructured":"Gambichler T, Abu Rached N, Tannapfel A, Becker JC, Vogt M, Skrygan M, Wieland U, Silling S, Susok L, St\u00fccker M, Meyer T, Stockfleth E, Junker K, K\u00e4fferlein HU, Br\u00fcning T, Lang K (2021b) Expression of mismatch repair proteins in Merkel cell carcinoma. Cancers 13(11):2524","journal-title":"Cancers"},{"issue":"7","key":"4002_CR9","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1158\/2159-8290.CD-20-0987","volume":"11","author":"G Germano","year":"2021","unstructured":"Germano G, Lu S, Rospo G, Lamba S, Rousseau B, Fanelli S, Stenech D, Le DT, Hays J, Totaro MG, Amodio V, Chil\u00e0 R, Mondino A, Diaz LA Jr, Di Nicolantonio F, Bardelli A (2021) CD4 T cell-dependent rejection of Beta-2 microglobulin null mismatch repair-deficient tumors. Cancer Discov 11(7):1844\u20131859","journal-title":"Cancer Discov"},{"issue":"1","key":"4002_CR10","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12957-017-1158-8","volume":"15","author":"AA Hashmi","year":"2017","unstructured":"Hashmi AA, Ali R, Hussain ZF, Faridi N, Khan EY, Bakar SMA, Edhi MM, Khan M (2017) Mismatch repair deficiency screening in colorectal carcinoma by a four-antibody immunohistochemical panel in Pakistani population and its correlation with histopathological parameters. World J Surg Oncol 15(1):116","journal-title":"World J Surg Oncol"},{"key":"4002_CR11","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1016\/j.humpath.2004.09.016","volume":"12","author":"M Korabiowska","year":"2004","unstructured":"Korabiowska M, Cordon-Cardo C, Jaenckel F, Stachura J, Fischer G, Brinck U (2004) Application of in situ hybridization probes for MLH-1 and MSH-2 in tissue microarrays of paraffin-embedded malignant melanomas: Correlation with immunohisto-chemistry and tumor stage. Hum Pathol 12:1543\u20131548","journal-title":"Hum Pathol"},{"key":"4002_CR12","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1097\/cmr.0000000000000298","volume":"26","author":"O Kube\u010dek","year":"2016","unstructured":"Kube\u010dek O, Kopeck\u00fd J (2016) Microsatellite instability in melanoma: a comprehensive review. Melanoma Res 26:545\u2013550. https:\/\/doi.org\/10.1097\/cmr.0000000000000298","journal-title":"Melanoma Res"},{"issue":"6439","key":"4002_CR13","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1126\/science.aau0447","volume":"364","author":"R Mandal","year":"2019","unstructured":"Mandal R, Samstein RM, Lee KW, Havel JJ, Wang H, Krishna C, Sabio EY, Makarov V, Kuo F, Blecua P, Ramaswamy AT, Durham JN, Bartlett B, Ma X, Srivastava R, Middha S, Zehir A, Hechtman JF, Morris LG, Weinhold N, Riaz N, Le DT, Diaz LA Jr, Chan TA (2019) Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response. Science 364(6439):485\u2013491","journal-title":"Science"},{"key":"4002_CR14","doi-asserted-by":"publisher","first-page":"12452","DOI":"10.18632\/oncotarget.23746","volume":"9","author":"R Marconcini","year":"2018","unstructured":"Marconcini R, Spagnolo F, Stucci LS et al (2018) Current status and perspectives in immunotherapy for metastatic melanoma. Oncotarget 9:12452\u201312470","journal-title":"Oncotarget"},{"key":"4002_CR15","first-page":"3","volume":"12","author":"G Ponti","year":"2020","unstructured":"Ponti G, Pellacani G, Tomasi A, Depenni R, Maccaferri M, Maiorana A, Orsi G, Giusti F, Cascinu S, Manfredini M (2020) Immuno-histochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response. Mol Clin Oncol 12:3\u20138","journal-title":"Mol Clin Oncol"},{"key":"4002_CR16","first-page":"341","volume":"26","author":"L Roncati","year":"2018","unstructured":"Roncati L (2018) Microsatellite instability predicts response to anti-PD1 immunotherapy in metastatic melanoma. Acta Dermatovenerol Croat ADC 26:341\u2013343","journal-title":"Acta Dermatovenerol Croat ADC"},{"key":"4002_CR17","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","volume":"392","author":"D Schadendorf","year":"2018","unstructured":"Schadendorf D, van Akkooi ACJ, Berking C et al (2018) Melanoma. Lancet 392:971\u2013984","journal-title":"Lancet"},{"key":"4002_CR18","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1093\/jnci\/djh034","volume":"96","author":"A Umar","year":"2004","unstructured":"Umar A, Boland CR, Terdiman JP et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261\u2013268","journal-title":"J Natl Cancer Inst"},{"issue":"4","key":"4002_CR19","doi-asserted-by":"publisher","first-page":"178","DOI":"10.32074\/1591-951X-113","volume":"112","author":"S Vatrano","year":"2020","unstructured":"Vatrano S, Pettinato A, Randazzo V, Zagami M, Agueli C, Cannella S, Banna GL, Fraggetta F, Santoro A (2020) Diagnostic test assessment. Validation study of an alternative system to detect microsatellite instability in colorectal carcinoma. Pathologica 112(4):178\u2013183","journal-title":"Pathologica"},{"key":"4002_CR20","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0887","author":"K Wang","year":"2022","unstructured":"Wang K, Patkar S, Lee JS, Gertz EM, Robinson W, Schischlik F, Crawford DR, Schaffer AA, Ruppin E (2022) Deconvolving clinically relevant cellular immune crosstalk from bulk gene expression using CODEFACS and LIRICS stratifies melanoma patients to anti-PD-1 therapy. Cancer Discov. https:\/\/doi.org\/10.1158\/2159-8290.CD-21-0887","journal-title":"Cancer Discov"},{"key":"4002_CR21","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.jid.2016.01.035","volume":"136","author":"DC Whiteman","year":"2016","unstructured":"Whiteman DC, Green AC, Olsen CM (2016) The growing burden of invasive melanoma: projections of incidence rates and numbers of new cases in six susceptible populations through 2031. J Invest Dermatol 136:1161\u20131171","journal-title":"J Invest Dermatol"},{"issue":"4","key":"4002_CR22","doi-asserted-by":"publisher","first-page":"651","DOI":"10.3390\/cancers13040651","volume":"13","author":"M Zhu","year":"2021","unstructured":"Zhu M, Jin Z, Hubbard JM (2021) Management of non-colorectal digestive cancers with microsatellite instability. Cancers 13(4):651","journal-title":"Cancers"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-04002-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-022-04002-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-022-04002-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T10:12:50Z","timestamp":1677838370000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-022-04002-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,13]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["4002"],"URL":"https:\/\/doi.org\/10.1007\/s00432-022-04002-4","relation":{},"ISSN":["0171-5216","1432-1335"],"issn-type":[{"type":"print","value":"0171-5216"},{"type":"electronic","value":"1432-1335"}],"subject":[],"published":{"date-parts":[[2022,4,13]]},"assertion":[{"value":"11 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"TG has received speakers and\/or advisory board honoraria from BMS, Sanofi-Genzyme, MSD, Novartis Pharma, Roche, Abbvie, Almirall, Janssen, Lilly, Pfizer, Pierre Fabre, Merck-Serono, outside the submitted work. JCB is receiving speaker\u2019s bureau honoraria from Amgen, Pfizer, Merck-Serono and Sanofi, is a paid consultant\/advisory board member for eTheRNA, Merck-Serono, Pfizer, 4SC and Sanofi. His group receives research grants from Bristol-Myers Squibb, Merck Serono, and Alcedis. LS has received speakers and\/or advisory board honoraria from BMS, Sun-Pharma, MSD, and Novartis. The other authors report no conflicts or competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This non-interventional study was approved by Institutional Review Board at the Ruhr-University Bochum (IRB Study ID #16-5985). All procedures performed in studies involving human participants or their data were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}