title: Imaging mass spectrometry of myxoid sarcomas identifies proteins and lipids specific to tumour type and grade, and reveals biochemical intratumour heterogeneity.
abstract: 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. 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.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Willems
authors.forename: Alexandra
authors.initials: A
authors.lastname: van Remoortere
authors.forename: René
authors.initials: R
authors.lastname: van Zeijl
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.forename: Liam A
authors.initials: LA
authors.lastname: McDonnell
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005354:Fibrosarcoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D018208:Liposarcoma, Myxoid / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins