[100] Intramuscular Myxoma and Grade I Myxofibrosarcoma Are Characterized by Distinct Genetic Alterations and Specific Composition of Their ECM

SM Willems, AB Mohseny, CI Balog, R Sewrajsing, I Briaire, AM Cleton-Jansen, R Sciot, CDM Fletcher, AM Deelder, K Szuhai, PJ Hensbergen, PCW Hogendoorn. LUMC, Leiden, Netherlands; University Hospitals, Leuven, Belgium; Brigham and Women's Hospital, Boston

Background: Intramuscular myxoma and grade I myxofibrosarcoma are mesenchymal tumours characterized by their abundant myxoid extracellular matrix (ECM). They show considerable histological overlap but differ in clinical behaviour. Therefore the differential diagnosis is important but can be challenging.
Design: We investigated the differences in genetic aberrations and composition of the ECM between both tumours. GNAS1 activating mutations have been described in intramuscular myxoma while till now, no reports are available for myxofibrosarcoma. Activating mutations in K-RAS, which might activate cFos in an alternative pathway, have never been studied in either intramuscular myxoma or myxofibrosarcoma. Well documented series of intramuscular myxoma (n=10) and grade I myxofibrosarcoma (n=10) cases were karyotyped, analysed for GNAS1 and K-RAS mutations and downstream activation of cFos mRNA and protein expression. Liquid chromatography mass spectrometry (LC-MS) of tumour lysates identified structural ECM proteins, such as collagen I, VI, XII, XIV and decorin, which we validated by immunohistochemistry and qPCR.
Results: Grade I myxofibrosarcoma showed variable, non-specific cytogenetic aberrations in 83,5 % of cases (n=6) reflecting intrinsic chromosomal instability, whereas karyotypes of intramuscular myxoma were all normal (n=7). GNAS1 activating mutations were exclusively found in 50% of intramuscular myxoma. Overexpression of downstream cFos mRNA and protein was found in both tumours. No mutations in K-RAS codon 12/13 were detected. LC-MS revealed many structural proteins in the ECM of grade I myxofibrosarcoma lacking in intramuscular myxoma. Decorin and collagen VI were expressed significantly higher in grade I myxofibrosarcoma compared to intramuscular myxoma at both mRNA and protein level.
Conclusions: We showed that intramuscular myxoma and grade I myxofibrosarcoma show different molecular genetic aberrations and specific composition of their ECM which probably contribute to their pathogenesis. GNAS1 mutation analysis can be helpful to distinguish intramuscular myxoma from grade I myxofibrosarcoma in some cases.
Category: Bone & Soft Tissue

Monday, March 9, 2009 9:30 AM

Poster Session I Stowell-Orbison/Autopsy Award # 20, Monday Morning