Mesenchymal-to-Endothelial Transition in Kaposi Sarcoma: A Histogenetic Hypothesis Based on a Case Series and Literature Review

Abstract

ObjectivesAlthough several studies have been conducted regarding Kaposi sarcoma (KS), its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature.MethodsIn 15 cases of KSs diagnosed during 2000–2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF), COX-2, c-KIT, smooth muscle antigen (SMA), and stem cell surface marker CD105.ResultsBoth CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs.ConclusionsKS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.

Tumor Endothelial Cells with Distinct Patterns of TGFβ-Driven Endothelial-to-Mesenchymal Transition

“…Though ZsGreen Cdh5-Cre mice are a high-fidelity EC lineage tracing model, it is also conceptually possible that SMA + fibroblasts or other mesenchymal-lineage cells may acquire EC markers through mesenchymal-endothelial transition (MEndT), which is a reverse process of EndMT. While EndMT has been observed in a wide range of conditions, the phenomenon of MEndT in tumors is still a matter of debate (33). In contrast to EndMT which may arise spontaneously in vitro, generation of EC from lineage-committed mesenchymal cells requires enforced induction of multiple EC-selective transcription factors in addition to TGFβ inhibition, indicating that MEndT demands restrictive conditions and precise temporal activation of specific regulatory factors (34).…”

Hepatitis B virus-associated intrahepatic cholangiocarcinoma: a malignancy of distinctive characteristics between hepatocellular carcinoma and intrahepatic cholangiocarcinoma

“…However, the publications could not provide any pathological evidence of this phenomenon and there was no further explanation. Gurzu et al [45] performed immunohistochemical staining on 15 Kaposi sarcoma specimens and found that human herpesvirus 8-modified pluripotent mesenchymal cells most likely transformed into vascular endothelial cells. More recently, a publication from Nature concluded that cardiac fibroblasts could be transformed into vascular endothelial cells, thereby participating in neovascularization after cardiac injury to improve cardiac function [46].…”

Nucleoside/nucleotide reverse transcriptase inhibitors attenuate angiogenesis and lymphangiogenesis by impairing receptor tyrosine kinases signalling in endothelial cells

“…Furthermore, mechanical investigations have shown that NRTIs cause mitochondrial dysfunction and oxidative stress in arterial endothelial cells (ECs) (Jiang et al, ). However, a number of studies have reported that antiviral treatment in HIV‐positive patients inhibited the occurrence and progression of Kaposi sarcoma, an AIDS‐defining illness characterized by an abundant growth of immature microvessels originating from the lymphatic endothelium (Beckstead et al, ) and mesenchymal–endothelial transitions (Gurzu et al, ). These clinical cases suggest NRTIs can have potent effects on angiogenesis and lymphangiogenesis.…”