Myxoid tumours of soft tissues are a heterogeneous group of mesenchymal origin characterized by their so-called myxoid extracellular matrix. although their histological overlap, their clinical... Show moreMyxoid tumours of soft tissues are a heterogeneous group of mesenchymal origin characterized by their so-called myxoid extracellular matrix. although their histological overlap, their clinical behaviour ranges form benign to malignant. In this thesis we studied the exact nature and possible function of the components of the myxoid matrix using a broad range of techniques (including (immuno)histochemistry and (imaging) mass spectrometry. Furthermore, we studied the molecular (cyto)genetic aberrations in different myxoid soft tissue tumours, using direct sequence analysis and COBRA FISH. Show less
Willems, S.M.; Remoortere, A. van; Zeijl, R. van; Deelder, A.M.; McDonnell, L.A.; Hogendoorn, P.C.W. 2010
Myxofibrosarcoma and myxoid liposarcomas are relatively common soft tissue tumours that are characterized by their so-called myxoid extracellular matrix and have to some extent overlap in histology... Show moreMyxofibrosarcoma and myxoid liposarcomas are relatively common soft tissue tumours that are characterized by their so-called myxoid extracellular matrix and have to some extent overlap in histology. The exact composition and potential role of their myxoid extracellular matrix are insufficiently understood. To gain more insight into the biomolecular content of these tumours, we have studied 40 well-documented myxofibrosarcoma and myxoid liposarcoma cases using imaging mass spectrometry. This technique provides a multiplex biomolecular imaging analysis of the tissue, spanning multiple molecular domains and without a priori knowledge of the tissue's biomolecular content. We have developed experimental protocols for analysing the peptide, protein, and lipid content of myxofibrosarcoma and myxoid liposarcomas, and have detected proteins and lipids that are tumour-type and tumour-grade specific. In particular, lipid changes observed in myxoid liposarcomas could be related to pathways known to be affected during tumour progression. Unsupervised clustering of the biomolecular signatures was able to classify myxofibrosarcoma and myxoid liposarcomas according to tumour type and tumour grade. Closer examination of histologically similar regions in the tissues revealed intratumour heterogeneity, which was a consistent feature in each of the myxofibrosarcomas studied. In intermediate-grade myxofibrosarcoma, it was found that single tissue sections could contain regions with biomolecular profiles similar to high-grade and low-grade tumours, and that these regions were associated with the tumour's nodular structure, thus supporting a concept of tumour progression through clonal selection. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Show less
