Ganglioside metabolism has been linked to the clinical and
biological behavior of human
neuroblastoma. This study investigated the importance of differences in complex "b"
ganglioside (GD1b, GT1b, and GQ1b; designated
CbG) expression in this
tumor.
Gangliosides of 74
neuroblastomas were analyzed by high-performance TLC. Associations of
CbG expression with known prognostic markers and with event-free survival (EFS) were evaluated. Higher
CbG expression characterized nonprogressive versus progressive
tumors (median 41% versus 18% of total
gangliosides; P = 0.001) and completely accounted for the observed higher overall "b" pathway
ganglioside expression (median 81% versus 68%; P = 0.003). In contrast, expression of the structurally simpler "b" pathway
gangliosides (GD2 and GD3) did not differ (median 31% versus 35%; P = 0.4). Absolute
CbG content differed even more (median 93 versus 29 nmol/g among nonprogressive versus progressive
tumors; P = 0.02) and was most striking in the case of GQ1b content (8-fold higher in nonprogressive
tumors). High
CbG (> or =35% of total
gangliosides) expression was strongly predictive of a favorable outcome in: (a) the entire study population (90% versus 60% EFS at 25 months; P = 0.001); and (b) among patients assigned a low-risk status by a either single genetic or
biochemical tumor marker (MYCN,
DNA, NSE, or
ferritin), or by both unamplified MYCN and
aneuploid DNA (22-28% difference in EFS at 25 months). These data suggest that high
tumor CbG content may substratify "good prognosis"
neuroblastoma patients, identifying patients at very low risk of relapse or death, and that the
biological roles of
CbG in
neuroblastoma will be of importance to define.