MOLECULAR-DETECTION OF GAUGE EXPRESSION IN PERIPHERAL-BLOOD AND BONE-MARROW - UTILITY AS A TUMOR-MARKER FOR NEUROBLASTOMA

The GAGE family of tumor-associated antigens is present in a,vide spec trum of human tumors but is highly restricted among normal tissues exc ept to the testis, By reverse transcription-PCR, GAGE expression was d etected in 55 of 67 neuroblastomas (NBs; 8 of 12 stage 1, 13 of 13 sta ge 2, 9 of 12 stage 3, 7 of 12 stage 4S, and 18 of 18 stage 4), 5 of 5 Ewing's and peripheral neuroectodermal tumors, and 11 of II tumor cel l lines (9 NBs, 1 peripheral neuroectodermal tumor, and 1 melanoma). I n contrast, 5 of 6 normal tissues (normal testis was positive), 18 of 18 NB-negative bone marrow (BM; 9 normal, 6 non-NE remission, and 3 st age-2 NE), and 9 of 10 NB-negative peripheral blood (PB; 9 normal and 1 stage 2B) were undetectable, In 18 patients with widespread NE under treatment, GAGE expression in paired samples of BM and PB was 89% con cordant, Both correlated strongly with disease measured by conventiona l methods, including marrow histology or immunocytology, bone scan, me ta-iodo-benzylguanidine scan, computed tomography/magnetic resonance i maging, and urine vanillymandelic acid/homovanillic acid, When serial samples from 14 patients with stage 4 NE were studied, BM from 7 of 7 patients at diagnosis and 14 of 14 patients (25 samples) on treatment were positive for GAGE, Thirteen patients were in continual remission off therapy, and their GAGE expression (12 BM and 9 PB) was undetectab le at follow-up, When compared to molecular detection of tyrosine hydr oxylase mRNA, GAGE may offer added sensitivity in detecting NE in both BM and PB, The GAGE family of antigens may be potential tumor markers of minimal residual disease.