{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:52Z","timestamp":1787029252801,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC\u2014the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p &lt; 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.<\/jats:p>","DOI":"10.3390\/ph14040324","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T04:13:51Z","timestamp":1617336831000},"page":"324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1804-5015","authenticated-orcid":false,"given":"Shatavisha","family":"Dasgupta","sequence":"first","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senada","family":"Koljenovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-4565","authenticated-orcid":false,"given":"Thierry","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Swagemakers","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Clinical Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"van der Hoeven","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Gynecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6642-3856","authenticated-orcid":false,"given":"Ronald","family":"van Marion","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Spek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Clinical Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-4485","authenticated-orcid":false,"given":"Helena","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert","family":"van Kemenade","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-1115","authenticated-orcid":false,"given":"Patricia","family":"Ewing-Graham","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s11912-019-0833-z","article-title":"New Directions in Vulvar Cancer Pathology","volume":"21","author":"Williams","year":"2019","journal-title":"Curr. 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