The ganglioside, GD2, as a circulating tumor biomarker for neuroblastoma

Background: GD2 is a ganglioside that is ubiquitously expressed in the
plasma membrane of neuroblastoma and is shed into the circulation.
Procedure: GD2 was measured with a high-pressure liquid
chromatography/tandem mass spectrometry assay in serum or plasma from 40
children without cancer (controls) and in biobanked samples from 128 (73
high-risk) children with neuroblastic tumors at diagnosis, 56 children
with relapsed neuroblastoma, 14 children with high-risk neuroblastoma
after treatment, and 8 to 12 children each with 10 other common childhood
cancers at diagnosis. Results: The C18 (18 carbon fatty acid) lipoform was
the predominant circulating form of GD2 in controls and in patients with
neuroblastoma. The median concentration of GD2 in children with high-risk
neuroblastoma at diagnosis was 167 nM (range, 16.1-1060 nM), which was
30-fold higher than the median concentration (5.6 nM) in controls. GD2 was
not elevated in serum from children with the differentiated neuroblastic
tumors, ganglioneuroma (n = 10) and ganglioneuroblastoma-intermixed
subtype (n = 12), and in children with 10 other childhood cancers. GD2
concentrations were significantly higher in serum from children with
MYCN-amplified tumors (P = 0.0088), high-risk tumors (P < 0.00001),
International Neuroblastoma Staging System (INSS) stage 4 tumors (P
< 0.00001), and in children who died (P = 0.034). Conclusions:
Circulating GD2 appears to be a specific and sensitive tumor biomarker for
highrisk/ high-stage neuroblastoma and may prove to be clinically useful
as a diagnostic or prognostic circulating tumor biomarker. GD2 will be
measured prospectively and longitudinally in children enrolled on a
high-risk neuroblastoma treatment trial to assess its ability to measure
response to treatment and predict survival.