The three-dimensional microvascular architecture of the human Kaposi sarcoma implanted in nude mice: A SEM corrosion casting study S. Sangiorgi a, ⁎ , T. Congiu b , A. Manelli b , R. Dell'Eva c , D.M. Noonan d a Department of Surgery, Neurosurgical Unit, University of Insubria, Viale Borri 57, 21100 Varese, Italy b Department of Human Morphology, University of Insubria, Varese, Italy c National Institute for Cancer Research, Genova, Italy d Department of Clinical and Biological Science, University of Insubria, Varese, Italy Received 9 February 2006; revised 6 June 2006; accepted 11 June 2006 Available online 22 August 2006 Abstract The human Kaposi sarcoma represents one of the most common skin lesions associated with AIDS. Its clinical presentation and anatomopathological structure seem to demonstrate a particularly rich vascularity. The latest therapies aim to limit its intrinsic angiogenic activity in an attempt to reduce vascular density and the formation of new vessels. For these reasons, we decided to study the microvascular architecture of Kaposi sarcoma in three dimensions. We used a corrosion casting technique applied to nude mice previously transplanted subcutaneously with human modified neoplastic Kaposi sarcoma cells. The cooption of host vessels made by the tumor was demonstrated by three-dimensional scanning electron microscopy (SEM) images. At high magnification several angiogenic patterns were observed in the form of potato-shaped vessels, sprouts, intussusceptions and mouse tailed end tipped capillaries along with some ultrastructural features such as intercellular extravasations and endothelial cell modifications. Our investigation allowed us to build a detailed map of tumor vasculature in human Kaposi sarcoma. Furthermore, this study want to shed light on the sharp morphological three-dimensional conformation of angiogenic sprouts so to be able to better understand their modifications occurred during time and after antiangiogenic experimental therapies, by now observed only by immunohistochemical or immunofluorescent assays. © 2006 Elsevier Inc. All rights reserved. Keywords: Human Kaposi sarcoma; Corrosion casting; Angiogenesis Introduction Kaposi sarcoma (KS) remains the most common neoplastic lesion associated with HIV infection (Aversa et al., 2005; Dezube et al., 2004; Mitsuyasu, 2000; Noy et al., 2005). One of the striking features is its highly vascularized nature evident both macroscopically (De Dobbeleer et al., 1987) and histologically, along with an inflammatory infiltrate and proliferation of spindle-shaped neoplastic cells. Although most explanted KS cells undergo senescence in vitro, the identification of an immortalized KS line KS-Imm (Albini et al., 1997) forming highly angiogenic tumors in vivo (Albini et al., 1999) has led to studies on the mechanism involved in the formation of new vessels and antiangiogenic strategies. Previous studies on the microvascular architecture of KS have been limited to two-dimensional histological analyses. Our aim was to create a three-dimensional topographic vascular map of Kaposi sarcoma so as to have a specific guide to interpret the vascular modifications occurring during tumor growth and following antiangiogenic therapies. The corrosion casting method, coupled with scanning electron microscopy study and micrometric analysis by neural adaptive stereo matching (Raspanti et al., 2005), filled the gap between two-dimensional histology and 3D tumor architecture by yielding three-dimensional images of the surface of luminal space of neoplastic blood vessels, imagined as unique elements freed from any other tissue (Busam et al., 1995; Fallowfield and Cook, 1991; Hodde and Nowell, 1980; Lametschwandtner et al., 1990; Murai et al., 1992; Murakami, Microvascular Research 72 (2006) 128 – 135 www.elsevier.com/locate/ymvre ⁎ Corresponding author. Fax: +39 0332263324. E-mail address: simo.med@libero.it (S. Sangiorgi). 0026-2862/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.mvr.2006.06.001