N-Glycomic Profiling of Pheochromocytomas and Paragangliomas Separates Metastatic and Nonmetastatic Disease.

Abstract

Context:

No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paragangliomas, may serve as a diagnostic tool.

Objective:

To identify differences in N-glycomic profiles of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas.

Setting:

This study was conducted at Helsinki University Hospital, University of Helsinki, and Glykos Finland Ltd. and included 16 pheochromocytomas and paragangliomas: 8 primary metastasized pheochromocytomas or paragangliomas and 8 nonmetastasized tumors.

Methods:

N-glycan structures were analyzed with matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of formalin-fixed, paraffin-embedded tissue samples.

Main Outcome Measure:

N-glycan profile of tumor tissue.

Results:

Four groups of neutral N-glycan signals were more abundant in metastasized tumors than in nonmetastasized tumors: complex-type N-glycan signals of cancer-associated terminal N-acetylglucosamine, multifucosylated glycans (complex fucosylation), hybrid-type N-glycans, and fucosylated pauci-mannose-type N-glycans. Three groups of acidic N-glycans were more abundant in metastasized tumors: multifucosylated glycans, acid ester-modified (sulfated or phosphorylated) glycans, and hybrid-type/monoantennary N-glycans. Fucosylation and complex fucosylation were significantly more abundant in metastasized paragangliomas and pheochromocytomas than in nonmetastasized tumors for individual tests but were over the false positivity critical rate, when adjusted for multiplicity testing.

Conclusions:

MALDI-TOF MS profiling of primary pheochromocytomas and paragangliomas can identify diseases with metastatic potential based on their different N-glycan profiles. Thus, malignancy-linked N-glycan structures may serve as potential diagnostic tools for pheochromocytomas and paragangliomas.

• Authors: Helena Leijon, Tuomas Kaprio, Annamari Heiskanen, Tero Satomaa, Jukka O Hiltunen, Markku M Miettinen, Johanna Arola, Caj Haglund
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 102 Issue 11 Pg. 3990-4000 (11 01 2017) ISSN: 1945-7197 [Electronic] United States
• PMID: 28938401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

• Polysaccharides

Topics

• Adrenal Gland Neoplasms (diagnosis, metabolism, pathology)
• Adult
• Aged
• Diagnosis, Differential
• Female
• Glycomics
• Glycosylation
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging (methods)
• Paraganglioma (diagnosis, metabolism, pathology)
• Pheochromocytoma (diagnosis, metabolism, pathology)
• Polysaccharides (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Young Adult