Molecular detection of GAGE expression in peripheral blood and bone marrow: utility as a tumor marker for neuroblastoma

Abstract

The GAGE family of tumor-associated antigens is present in a wide spectrum of human tumors but is highly restricted among normal tissues except to the testis. By reverse transcription-PCR, GAGE expression was detected in 55 of 67 neuroblastomas (NBs; 8 of 12 stage 1, 13 of 13 stage 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 11 tumor cell lines (9 NBs, 1 peripheral neuroectodermal tumor, and 1 melanoma). In contrast, 5 of 6 normal tissues (normal testis was positive), 18 of 18 NB-negative bone marrow (BM; 9 normal, 6 non-NB remission, and 3 stage-2 NB), and 9 of 10 NB-negative peripheral blood (PB; 9 normal and 1 stage 2B) were undetectable. In 18 patients with widespread NB under treatment, GAGE expression in paired samples of BM and PB was 89% concordant. Both correlated strongly with disease measured by conventional methods, including marrow histology or immunocytology, bone scan, meta-iodo-benzylguanidine scan, computed tomography/magnetic resonance imaging, and urine vanilly-mandelic acid/homovanillic acid. When serial samples from 14 patients with stage 4 NB 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 undetectable at follow-up. When compared to molecular detection of tyrosine hydroxylase mRNA, GAGE may offer added sensitivity in detecting NB in both BM and PB. The GAGE family of antigens may be potential tumor markers of minimal residual disease.