Original Articles: Basic ScienceVascular endothelial growth factor/semaphorin-3A ratio and SEMA3A expression in cutaneous malignant melanomaLucarini, Guendalinaa; Simonetti, Orianab; Lazzarini, Raffaellaa; Giantomassi, Federicac; Goteri, Gaiac; Offidani, AnnamariabAuthor Information aDepartment of Clinic and Molecular Sciences, Histology bDermatological Clinic cUnit of Pathologic Anatomy and Histopathology, Polytechnic University of Marche Region, United Ancona Hospitals, Torrette, Ancona, Italy Received 20 September 2019 Accepted 30 April 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.melanomaresearch.com. Correspondence to Guendalina Lucarini, PhD, Università Politecnica delle Marche, Dipartimento di Scienze Cliniche e Molecolari-Istologia, Via Tronto 10/a 60020 Torrette, Ancona, Italy, Tel: +39 712206075; fax: +39 712206203; e-mail: firstname.lastname@example.org Melanoma Research: October 2020 - Volume 30 - Issue 5 - p 433-442 doi: 10.1097/CMR.0000000000000674 Buy SDC Metrics Abstract Breslow thickness and Clark level are still important factors for cutaneous melanoma, but do not provide a precise prognosis in all cases. It is necessary to find new factors capable of a more accurate prediction of the tumor course. Angiogenesis is essential for tumor development and progression and is regulated by vascular endothelial growth factor A (VEGF-A) and semaphorins (SEMA), in particular, SEMA3A inhibits angiogenesis by affecting VEGF signaling. However, the prognostic role of angiogenetic factors remains unclear. To date, no information is available on SEMA3A in human melanoma. Microvessel density, immunohistochemical and mRNA VEGF and SEMA3A expression level in 60 thin (Breslow thickness ≤ 1.0 mm), 60 intermediate (1.1–4.0 mm) and 50 thick (>4.0 mm) primary human cutaneous melanomas were investigated and related to clinical/pathological parameters and disease-specific survival. No positive association between Breslow thickness, Clark level, metastasis presence and survival was identified; Clark level was poorly related to survival. VEGF and microvessel density were significantly higher in intermediate and thick melanomas and related to Breslow thickness and Clark level but not to metastasis status and survival. On the contrary, SEMA3A was significantly reduced in intermediate and thick melanomas and associated to metastasis and poor survival. VEGF/SEMA3A ratio was higher in the worst prognosis, resulting the most closely related factor with metastasis and survival. SEMA3A expression and VEGF/SEMA3A ratio turned out to be valuable prognostic biomarkers in patients affected by cutaneous melanoma, in particular with Breslow thickness >1 mm. SEMA3A might serve as a candidate tumor suppressor in cutaneous melanoma therapy. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.