Molecular signatures of tumor progression in myxoid liposarcoma identified by N-glycan mass spectrometry imaging.

Bram Heijs, Stephanie Holst-Bernal, Marieke A de Graaff, Inge H Briaire-de Bruijn, Mar Rodriguez-Girondo, Michiel A J van de Sande, Manfred Wuhrer, Liam A McDonnell, Judith V M G Bovée

Laboratory investigation; a journal of technical methods and pathology 2020 Sep

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Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, accounting for ~6% of all sarcomas. MLS is characterized by a pathognomonic FUS-DDIT3, or rarely EWSR1-DDIT3, gene fusion. The presence of ≥5% hypercellular round cell areas is associated with a worse prognosis for the patient and is considered high grade. The prognostic significance of areas with moderately increased cellularity (intermediate) is currently unknown. Here we have applied matrix-assisted laser desorption/ionization mass spectrometry imaging to analyze the spatial distribution of N-linked glycans on an MLS microarray in order to identify molecular markers for tumor progression. Comparison of the N-glycan profiles revealed that increased relative abundances of high-mannose type glycans were associated with tumor progression. Concomitantly, an increase of the average number of mannoses on high-mannose glycans was observed. Although overall levels of complex-type glycans decreased, an increase of tri- and tetra-antennary N-glycans was observed with morphological tumor progression and increased tumor histological grade. The high abundance of tri-antennary N-glycan species was also associated with poor disease-specific survival. These findings mirror recent observations in colorectal cancer, breast cancer, ovarian cancer, and cholangiocarcinoma, and are in line with a general role of high-mannose glycans and higher-antennary complex-type glycans in cancer progression.

Citation

Bram Heijs, Stephanie Holst-Bernal, Marieke A de Graaff, Inge H Briaire-de Bruijn, Mar Rodriguez-Girondo, Michiel A J van de Sande, Manfred Wuhrer, Liam A McDonnell, Judith V M G Bovée. Molecular signatures of tumor progression in myxoid liposarcoma identified by N-glycan mass spectrometry imaging. Laboratory investigation; a journal of technical methods and pathology. 2020 Sep;100(9):1252-1261