{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:35:55Z","timestamp":1760236555338,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000654","name":"Marie Curie","doi-asserted-by":"publisher","award":["H2020-MSCA-RISE-2018, ID 777682-CANCER","H2020-MSCA-RISE 2019, ID 872860-PRISAR2","H2020-WIDESPREAD-2018-Twinning 852985-SIMICA"],"award-info":[{"award-number":["H2020-MSCA-RISE-2018, ID 777682-CANCER","H2020-MSCA-RISE 2019, ID 872860-PRISAR2","H2020-WIDESPREAD-2018-Twinning 852985-SIMICA"]}],"id":[{"id":"10.13039\/501100000654","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bontiusstichting \u2013 LUMC","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Surgical removal of vulvar squamous cell carcinoma (VSCC) is associated with significant morbidity and high recurrence rates. This is at least partially related to the limited visual ability to distinguish (pre)malignant from normal vulvar tissue. Illumination of neoplastic tissue based on fluorescent tracers, known as fluorescence-guided surgery (FGS), could help resect involved tissue and decrease ancillary mutilation. To evaluate potential targets for FGS in VSCC, immunohistochemistry was performed on paraffin-embedded premalignant (high grade squamous intraepithelial lesion and differentiated vulvar intraepithelial neoplasia) and VSCC (human papillomavirus (HPV)-dependent and -independent) tissue sections with healthy vulvar skin as controls. Sections were stained for integrin \u03b1v\u03b26, CAIX, CD44v6, EGFR, EpCAM, FR\u03b1, MRP1, MUC1 and uPAR. The expression of each marker was quantified using digital image analysis. H-scores were calculated and percentages positive cells, expression pattern, and biomarker localization were assessed. In addition, tumor-to-background ratios were established, which were highest for (pre)malignant vulvar tissues stained for integrin \u03b1v\u03b26. In conclusion, integrin \u03b1v\u03b26 allowed for the most robust discrimination of VSCCs and adjacent premalignant lesions compared to surrounding healthy tissue in immunohistochemically stained tissue sections. The use of an \u03b1v\u03b26 targeted near-infrared fluorescent probe for FGS of vulvar (pre)malignancies should be evaluated in future studies.<\/jats:p>","DOI":"10.3390\/cancers13236006","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T22:50:45Z","timestamp":1638226245000},"page":"6006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrin \u03b1v\u03b26 as a Target for Tumor-Specific Imaging of Vulvar Squamous Cell Carcinoma and Adjacent Premalignant Lesions"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-0658","authenticated-orcid":false,"given":"Bertine W.","family":"Huisman","sequence":"first","affiliation":[{"name":"Center for Human Drug Research, 2333 CL Leiden, The Netherlands"},{"name":"Department of Gynecology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Cankat","sequence":"additional","affiliation":[{"name":"Center for Human Drug Research, 2333 CL Leiden, The Netherlands"},{"name":"Department of Gynecology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tjalling","family":"Bosse","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander L.","family":"Vahrmeijer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Rissmann","sequence":"additional","affiliation":[{"name":"Center for Human Drug Research, 2333 CL Leiden, The Netherlands"},{"name":"Leiden Academic Center for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacobus","family":"Burggraaf","sequence":"additional","affiliation":[{"name":"Center for Human Drug Research, 2333 CL Leiden, The Netherlands"},{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Leiden Academic Center for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4337-2758","authenticated-orcid":false,"given":"Cornelis F. M.","family":"Sier","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Percuros BV, 2333 CL Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariette I. E.","family":"van Poelgeest","sequence":"additional","affiliation":[{"name":"Center for Human Drug Research, 2333 CL Leiden, The Netherlands"},{"name":"Department of Gynecology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ygyno.2020.01.029","article-title":"Trends in HPV-dependent and HPV-independent vulvar cancers: The changing face of vulvar squamous cell carcinoma","volume":"157","author":"Eva","year":"2020","journal-title":"Gynecol. 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