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This study examined whether equine SCC contains endothelial-like tumor cells forming vasculogenic mimicry (VM). Histopathology, PAS/CD31 profiling, and triple immunofluorescence (CD31, pan-cytokeratin, and collagen IV or αSMA) identified VM in 13 lesions. EcPV type 2 was detected in all genital and half of oronasal tumors, supporting a possible viral association and suggesting VM-cancer cells recruit pericytes to stabilize channels.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/detection-of-vasculogenic-mimicry-in-equine-ocular-oronasal-and-genital-squamous-cell-carcinoma/353497/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/detection-of-vasculogenic-mimicry-in-equine-ocular-oronasal-and-genital-squamous-cell-carcinoma/353497.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is vasculogenic mimicry (VM) and why was it investigated in equine SCC?","Question",{"text":113,"@type":114},"VM refers to endothelial-like tumor cell structures forming pseudo-vessels. It was investigated because equine SCC is difficult to treat and key aspects of tumor progression and metastasis remain unclear.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were equine SCC tissues tested to detect VM?",{"text":118,"@type":114},"Tumors were diagnosed histopathologically, then evaluated using Periodic Acid-Schiff (PAS) reaction and immunohistochemical staining for CD31. Lesions with PAS-positive, CD31-negative lumens containing erythrocytes were then confirmed with triple immunofluorescence for CD31, pan-cytokeratin, and type 4 collagen or αSMA.",{"name":120,"@type":111,"acceptedAnswer":121},"What role did EcPV infection and pericytes seem to have in this study?",{"text":122,"@type":114},"EcPV type 2 was found in all genital and 50% of oronasal lesions, while ocular lesions were negative. Protein detection in the context of VM suggested that VM-forming cancer cells recruit pericytes to enhance channel formation and stability.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},353497,1790206140,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","OPEN ACCESS  \nCitation: Schwarz S, Kummer S, Klang A, Walter I, Nell B, Brandt S (2026) Detection of vasculogenic mimicry in equine ocular, oronasal, and genital squamous cell carcinoma. PLoS One 21(1): e0328584. [https://doi](https://doi). org/10.1371/journal.pone.0328584  \nEditor: Gayle E. Woloschak, Northwestern University Feinberg School of Medicine, UNITED STATES OF AMERICA  \nReceived: July 22, 2025  \nAccepted: December 12, 2025  \nPublished: January 5, 2026  \nCopyright: © 2026 Schwarz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nData availability statement: All relevant data are within the paper and its Supporting  Information files.  \nFunding: The author(s) received no specific funding for this work.  \nRESEARCH ARTICLE  \nDetection of vasculogenic mimicry in equine ocular, oronasal, and genital squamous cell carcinoma  \nSophie Schwarz1, Stefan Kummer2, Andrea Klang3, Ingrid Walter2,4, Barbara Nell1, Sabine Brandt5*  \n1 Department for Small Animals and Horses, University of Veterinary Medicine, Vienna, Austria, 2 VetCore Facility for Research, University of Veterinary Medicine, Vienna, Austria, 3 Institute of Pathology, Department of Biological Sciences and Pathobiology, University of Veterinary Medicine, Vienna, Austria, 4 Institute of Morphology, Department of Biological Sciences and Pathobiology, University of Veterinary Medicine, Vienna, Austria, 5 Research Group Oncology, Division of Equine Surgery, Department for Small Animal and Horses, University of Veterinary Medicine, Vienna, Austria  \n* [sabine.brandt@vetmeduni.ac.at](sabine.brandt@vetmeduni.ac.at)  \nAbstract  \nSquamous cell carcinoma (SCC) is the most common malignant tumor disease in horses. It predominantly affects the ocular, oronasal, and anogenital region. Equine SCC is difficult to treat, also because important aspects of SCC development and metastasis are still unclear. We previously provided evidence that equine SCC cells can adopt a stem cell-like phenotype as a hallmark of malignant progression. Here, we investigated whether equine SCCs harbor endothelial-like tumor cells that forman alternative network of pseudo-vessels better known as vasculogenic mimicry (VM) . Following histopathological diagnosis, 43 equine SCCs or precursor lesions (15 ocular, 14 genital, 14 oronasal tumors) were PCR-screened for equine papillomavirus (EcPV) infection. Subsequently, formalin-fixed paraffin-embedded (FFPE)-sections of all tumors were analyzed by Periodic Acid-Schiff (PAS) reaction and immunohistochemical (IHC) staining for endothelial cell marker CD31 . Obtained micrographs were evaluated by a scientific board to unanimously identify sections of intact tumor tissue displaying PAS-positive, CD31-negative lumens harboring erythrocytes. Thirteen lesions exhibiting these features were subjected to triple immunofluorescence (IF) staining for CD31, pan-cytokeratin (KRT) and type 4 collagen (Col4) or alpha smooth muscle actin (αSMA) to confirm the presence of VM, and to determine whether pericytes have a role in this phenomenon. All genital and 50% of oronasal lesions scored positive for EcPV type 2, whilst ocular lesions tested negative. One mandibular SCCharbored EcPV type 5. Six genital, three oronasal, and four ocular tumors unambiguously exhibited VM as revealed by CD31-/PAS+ vessel-like structures containing erythrocytes, the detection of CD31-negative cells lining their lumens, and the presence of Col4 and αSMA in this lining. Detection of these two proteins in the context  \nPLOS One | [https://doi.org/10.1371/journal.pone.0328584](https://doi.org/10.1371/journal.pone.0328584) January 5, 2026 1 / 17  \nCompeting interests: The authors have declared that no competing interests exist.  \nof VM suggests that VM-forming cancer cells recruit pericytes to enhance channel for","cbCaikqX6WwmJCiJ","https://ap.wps.com/l/cbCaikqX6WwmJCiJ","pdf",3767247,17,"English","# Abstract\n# Introduction","[{\"question\":\"What is vasculogenic mimicry (VM) and why was it investigated in equine SCC?\",\"answer\":\"VM refers to endothelial-like tumor cell structures forming pseudo-vessels. It was investigated because equine SCC is difficult to treat and key aspects of tumor progression and metastasis remain unclear.\"},{\"question\":\"How were equine SCC tissues tested to detect VM?\",\"answer\":\"Tumors were diagnosed histopathologically, then evaluated using Periodic Acid-Schiff (PAS) reaction and immunohistochemical staining for CD31. Lesions with PAS-positive, CD31-negative lumens containing erythrocytes were then confirmed with triple immunofluorescence for CD31, pan-cytokeratin, and type 4 collagen or αSMA.\"},{\"question\":\"What role did EcPV infection and pericytes seem to have in this study?\",\"answer\":\"EcPV type 2 was found in all genital and 50% of oronasal lesions, while ocular lesions were negative. Protein detection in the context of VM suggested that VM-forming cancer cells recruit pericytes to enhance channel formation and stability.\"}]","Detection of vasculogenic mimicry in equine ocular, oronasal, and genital squamous cell carcinoma | PDF",1790105773,43]