Levels of specific serum N-glycans identify breast cancer patients with higher circulating tumor cell counts

Background: Metastatic breast cancer (MBC) is currently an incurable condition that is primarily treated with palliative measures. Isolation of circulating tumor cells (CTCs) from the peripheral blood of these patients provides a predictive prognostic indicator, independent of the type of therapy, site of occurrence and biological characteristics of the primary disease. It has been well established that glycosylation processing pathways are disturbed in cancer, leading to alterations in the glycan content of glycoproteins. Materials and methods: The bi-, tri- and tetraantennary glycans containing sialyl Lewis x (sLe^x) epitopes (A2F1G1, A3F1G1, A4F1G1 and A4F2G2) were quantified using normal phase high-performance liquid chromatography in combination with exoglycosidase array digestions in the glycan pools released from sera of 27 patients with advanced breast cancer (16 with CTCs <5/7.5 ml and 11 with CTCs ≥5/7.5 ml) and 13 healthy women. Results: The levels of all these glycans were significantly higher in patients with CTCs ≥5/7.5 ml compared with patients with CTCs <5/7.5 ml. Conclusions: As high levels of glycans containing sLe^x epitopes were associated with CTCs, their measurement may provide a new noninvasive approach for determining prognosis in women with MBC. The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.