Abstract

Human angiosarcoma (AS) is an infrequent soft tissue malignancy that may be difficult to diagnose, especially the solid, epithelioid or pleomorphic variant. A broad panel of antibodies is often necessary to determine the phenotype by Immunohistochemistry (IHC). To improve our knowledge of the morphology, immunophenotype, genetics and molecular biology, we constructed an in vivo xenograft platform using human soft tissue AS in nude mice. Tissue Microarrays (TMAs) were built from the original tumors and subsequent passages. The study included four original human AS, plus one secondary (a primary Malignant Peripheral Nerve Sheath Tumor (MPNST) which became an angiosarcoma), followed over successive tumor transfers for several generations. Endothelial marker expression (CD31, CD34, FVIII, CD105 (endoglin), Caveolin (CAV-1), D2-40, V-cadherin, FLI1 and ERG n-terminal) was evaluated by IHC. Molecular and cytogenetics studies were also performed. Only three out of the five AS (60%), grew in nude mice. Between 30 and 52 passages were achieved. Cytogenetically, the tumors showed complex karyotypes with many clonal numerical and structural abnormalities. Molecular biology showed p53 wild-type and KDR in all the cases. The WWTR1-CAMTA fusion was absent, which may be helpful in distinguishing epithelioid AS from epithelioid hemangioendothelioma (EHE), as it has been described as a hallmark in the latter. CD31, ERG, D2-40 and V-cadherin were the most sensitive, and ERG and FLI1 the most specific markers in the present series. This is the first study to combine nude mice xenografts and TMA studies in human AS, and describes for the first time an angiosarcomatous differentiation of an MPNST which occurred during the late passages generating a Kasabach-Merritt-like syndrome in the animal.

Keywords: Angiosarcoma; Immunohistochemistry; MPNST; Tissue microarray; Xenografts