{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T18:51:26Z","timestamp":1787251886409,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Several histopathological risk factors have been examined in vulvar cancer (VC) so far. However, the prognostic relevance of morphological biomarkers such as tumor budding (TB) and poorly defined clusters (PDCs) remains to be determined. Material and Methods: We histologically analyzed the formation of peritumoral and intratumoral TB and PDCs in a cohort of 157 patients with VC. We assessed their association with clinico-pathological features and evaluated their prognostic impact in terms of the risk of local recurrence and occurrence of metastasis (Fisher\u2019s exact test) as well as overall survival (Log-rank test). Results: We determined a distinct prognostic relevance of peritumoral TB with regard to occurrence of metastasis (Fisher\u2019s exact test; p = 0.0415) as well as a significant reduced risk of local recurrence in the group with absent intratumoral TB (Fisher\u2019s exact test; p = 0.0004). Furthermore, we showed that patients without peritumoral budding formation had a significant superior prognosis in terms of overall survival (p = 0.0366, x2 = 4.370). Conclusions: This study shows that several new histomorphological biomarkers may serve useful in predicting the clinical course of patients with VC, identifying patients at a lower risk of developing metastases\/local recurrence as well as improved overall survival.<\/jats:p>","DOI":"10.3390\/cancers17101718","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:05:17Z","timestamp":1747800317000},"page":"1718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Tumor Budding and Poorly Defined Clusters as Histological Biomarkers in Squamous Cell Carcinomas of the Vulva"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5358-2751","authenticated-orcid":false,"given":"Gilbert Georg","family":"Klamminger","sequence":"first","affiliation":[{"name":"Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS), 66424 Homburg, Germany"},{"name":"Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1055-7249","authenticated-orcid":false,"given":"Annick","family":"Bitterlich","sequence":"additional","affiliation":[{"name":"Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS), 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bashar","family":"Haj Hamoud","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center (UKS), 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich-Franz","family":"Solomayer","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center (UKS), 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ertz","sequence":"additional","affiliation":[{"name":"Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS), 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Schn\u00f6der","sequence":"additional","affiliation":[{"name":"Saarland University Medical Center for Tumor Diseases (UTS), Saarland University (USAAR), 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8759-4371","authenticated-orcid":false,"given":"Bernd","family":"Holleczek","sequence":"additional","affiliation":[{"name":"Saarland Cancer Registry, 66117 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walburgis","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-4968","authenticated-orcid":false,"given":"Annette","family":"Hasenburg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS), 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3865-6833","authenticated-orcid":false,"given":"Meletios P.","family":"Nigdelis","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center (UKS), 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1053\/j.semdp.2020.09.004","article-title":"A Review of Prognostic Factors in Squamous Cell Carcinoma of the Vulva: Evidence from the Last Decade","volume":"38","author":"Julia","year":"2021","journal-title":"Semin. 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