High-risk gastrointestinal stromal tumour (GIST) and synovial sarcoma display similar angiogenic profiles: a nude mice xenograft study

摘要

Background: Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract.Spindle cell monophasic synovial sarcoma (SS) can be morphologically similar. Angiogenesis is a major factor for tumour growth andmetastasis. Our aim was to compare the angiogenic expression profiles of high-risk GIST and spindle cell monophasic SS by histological,immunohistochemical and molecular characterisation of the neovascularisation established between xenotransplanted tumours and thehost during the initial phases of growth in nude mice.Methods: The angiogenic profile of two xenotransplanted human soft-tissue tumours were evaluated in 15 passages in nude mice usingtissue microarrays (TMA). Tumour pieces were also implanted subcutaneously on the backs of 14 athymic Balb-c nude mice. The animalswere sacrificed at 24, 48, and 96 h; and 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecularstudies (neovascularisation experiments).Results: Morphological similarities were apparent in the early stages of neoplastic growth of these two soft-tissue tumours throughoutthe passages in nude mice and in the two neovascularisation experiments. Immunohistochemistry demonstrated overexpression of proangiogenicfactors between 24 h and 96 h after xenotransplantation in both tumours. Additionally, neoplastic cells coexpressed chemokines(CXCL9, CXCL10, GRO, and CXCL12) and their receptors in both tumours. Molecular studies showed two expression profiles, revealingan early and a late phase in the angiogenic process.Conclusion: This model could provide information on the early stages of the angiogenic process in monophasic spindle cell SS andhigh-risk GIST and offers an excellent way to study possible tumour response to antiangiogenic drugs.