{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:16:59Z","timestamp":1760235419072,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC &lt; 2 mm thickness and low-level MLH1, three patients with primary cSCC &gt; 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen\u2019s disease, cSCC &lt; 2 mm, cSCC &gt; 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer.<\/jats:p>","DOI":"10.3390\/curroncol28050287","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T09:53:23Z","timestamp":1630058003000},"page":"3316-3322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7862-3695","authenticated-orcid":false,"given":"Thilo","family":"Gambichler","sequence":"first","affiliation":[{"name":"Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4327-4936","authenticated-orcid":false,"given":"Nomun","family":"Ganjuur","sequence":"additional","affiliation":[{"name":"Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Tannapfel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Vogt","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Ruhr-University Bochum, 44789 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Scholl","sequence":"additional","affiliation":[{"name":"Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6853-0743","authenticated-orcid":false,"given":"Nessr","family":"Abu Rached","sequence":"additional","affiliation":[{"name":"Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Bruckm\u00fcller","sequence":"additional","affiliation":[{"name":"Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Skrygan","sequence":"additional","affiliation":[{"name":"Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-653X","authenticated-orcid":false,"given":"J\u00fcrgen C.","family":"Becker","sequence":"additional","affiliation":[{"name":"Translational Skin Cancer Research, German Cancer Consortium (DKTK) Partner Site Essen\/D\u00fcsseldorf, Department of Dermatology, University Duisburg-Essen, 47057 Essen, Germany"},{"name":"Translational Skin Cancer Research, DKTK Site Essen, ED03, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-4979","authenticated-orcid":false,"given":"Heiko U.","family":"K\u00e4fferlein","sequence":"additional","affiliation":[{"name":"Institute for Prevention and Occupational Medicine of the German Social Accident Insurances, Ruhr-University Bochum (IPA), 44789 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Br\u00fcning","sequence":"additional","affiliation":[{"name":"Institute for Prevention and Occupational Medicine of the German Social Accident Insurances, Ruhr-University Bochum (IPA), 44789 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute for Prevention and Occupational Medicine of the German Social Accident Insurances, Ruhr-University Bochum (IPA), 44789 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1038\/s41598-021-83502-8","article-title":"The incidence and clinical analysis of non-melanoma skin cancer","volume":"11","author":"Lange","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s11654-019-0144-8","article-title":"Fortgeschrittene Basalzell- und Plattenepithelkarzinome der Haut","volume":"6","author":"Gambichler","year":"2019","journal-title":"Best Pract. Onkol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wessely, A., Steeb, T., Leiter, U., Garbe, C., Berking, C., and Heppt, M.V. (2020). Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239300"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gilson, P., Merlin, J.L., and Harl\u00e9, A. (2021). Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA). Cancers, 13.","DOI":"10.3390\/cancers13071491"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/j.1365-2133.2009.09550.x","article-title":"Expression of DNA mismatch repair proteins and MSH2 polymorphisms in nonmelanoma skin cancers of organ transplant recipients","volume":"162","author":"Perrett","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.prp.2007.08.009","article-title":"Mutations of microsatellite instability target genes in sporadic basal cell carcinomas","volume":"203","author":"Saetta","year":"2007","journal-title":"Pathol. Res. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1600-6143.2009.02862.x","article-title":"No evidence for microsatellite instability in immunodeficiency-related skin cancers","volume":"10","author":"Borie","year":"2010","journal-title":"Am. J. Transplant."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1038\/jid.2008.397","article-title":"Azathioprine-induced microsatellite instability is not observed in skin carcinomas of organ transplant recipients","volume":"129","author":"Wisgerhof","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","first-page":"751","article-title":"Defects in DNA mismatch repair do not account for early-onset basal cell carcinoma","volume":"159","author":"Mosterd","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_10","first-page":"178","article-title":"Diagnostic test assessment. Validation study of an alternative system to detect microsatellite instability in colorectal carcinoma","volume":"112","author":"Vatrano","year":"2020","journal-title":"Pathol. J. Ital. Soc. Anat. Pathol. Diagn. Cytopathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/jid.2011.326","article-title":"Absence of mismatch repair deficiency-related microsatellite instability in non-melanoma skin cancer","volume":"132","author":"Reuschenbach","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_12","first-page":"59","article-title":"Evidence that dysregulated DNA mismatch repair characterizes human nonmelanoma skin cancer","volume":"158","author":"Young","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/1346-8138.12949","article-title":"Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions","volume":"42","author":"Hatta","year":"2015","journal-title":"J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1007\/s004280100445","article-title":"Reduced human mismatch repair protein expression in the development of precancerous skin lesions to squamous cell carcinoma","volume":"439","author":"Liang","year":"2001","journal-title":"Virchows Arch."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.humpath.2004.09.016","article-title":"Application of in situ hybridization probes for MLH-1 and MSH-2 in tissue microarrays of paraffin-embedded malignant melanomas: Correlation with immunohistochemistry and tumor stage","volume":"35","author":"Korabiowska","year":"2004","journal-title":"Hum. Pathol."},{"key":"ref_16","first-page":"3","article-title":"Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response","volume":"12","author":"Ponti","year":"2020","journal-title":"Mol. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gambichler, T., Abu Rached, N., Tannapfel, A., Becker, J.C., Vogt, M., Skrygan, M., Wieland, U., Silling, S., Susok, L., and St\u00fccker, M. (2021). Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13112524"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:53:13Z","timestamp":1760165593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,27]]},"references-count":17,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["curroncol28050287"],"URL":"https:\/\/doi.org\/10.3390\/curroncol28050287","relation":{},"ISSN":["1718-7729"],"issn-type":[{"type":"electronic","value":"1718-7729"}],"subject":[],"published":{"date-parts":[[2021,8,27]]}}}