GD2 synthase - A new molecular marker for detecting neuroblastoma

BACKGROUND. Neuroblastomas (NBs) almost ubiquitously express the gangliosid e GD2. GD2 synthesis is dependent on the key enzyme GD2 synthase. Thus, GD2 synthase transcript may prove to be a potential molecular marker of NB. METHODS. Seventy-seven NB tumor tissues of all stages, 5 NB cell tines, and 26 normal bone marrows (BMs) and peripheral blood (PBL) samples, as well a s 26 non-NB remission-Bids were analyzed for the expression of GD2 synthase by a highly sensitive reverse transcriptase-polymerise chain reaction (RT- PCR) and chemiluminescence detection. One hundred fifty-two NB BMs were tes ted and comparisons were made among three independent detection techniques, namely GD2 synthase RT-PCR, immunofluorescence (IF), and histology (HIST). RESULTS. GD2 synthase transcript was present in 5 of 5 cell lines and in 77 of 77 tumors tested. Among 116 marrows that were positive by at least 1 of the 3 methods, 78% were detectable by GD2 synthase, 68% by IF, and 46% by HIST. Seventy-six percent of positive BMs that were obtained during treatme nt and follow-up had GD2 synthase expression, whereas only 29% were HIST po sitive. Correlation between RT-PCR and IF was high (P = 0.001), and positiv ity by 3 out of 3 methods was strongly correlated with poor survival (P < 0 .01). Of note, marrows tested at the time of chemotherapy were positive by at least 2 out of 3 methods and were associated with adverse outcome (P = 0 .01). Serial samples (n = 28) in 5 patients demonstrated close agreement be tween RT-PCR and patient disease status. CONCLUSIONS. The current study found that molecular detection of GD2 syntha se transcript in NB BMs may have potential value in detecting rare tumor ce lls. (C) 2001 American Cancer Society.