| Summary: | The particularly high mortality of epithelial ovarian cancer (EOC) is in part linked to limited understanding of its molecular signatures. Although there are data available on in situ <i>N</i>-glycosylation in EOC tissue, previous studies focused primarily on neutral <i>N</i>-glycan species and, hence, still little is known regarding EOC tissue-specific sialylation. In this proof-of-concept study, we implemented MALDI mass spectrometry imaging (MALDI-MSI) in combination with sialic acid derivatization to simultaneously investigate neutral and sialylated <i>N</i>-glycans in formalin-fixed paraffin-embedded tissue microarray specimens of less common EOC histotypes and non-malignant borderline ovarian tumor (BOT). The applied protocol allowed detecting over 50 <i>m/z</i> species, many of which showed differential tissue distribution. Most importantly, it could be demonstrated that α2,6- and α2,3-sialylated <i>N</i>-glycans are enriched in tissue regions corresponding to tumor and adjacent tumor-stroma, respectively. Interestingly, analogous <i>N</i>-glycosylation patterns were observed in tissue cores of BOT, suggesting that regio-specific <i>N</i>-glycan distribution might occur already in non-malignant ovarian pathologies. All in all, our data provide proof that the combination of MALDI-MSI and sialic acid derivatization is suitable for delineating regio-specific <i>N</i>-glycan distribution in EOC and BOT tissues and might serve as a promising strategy for future glycosylation-based biomarker discovery studies.
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