Detection of microscopic disease: Comparing histology, immunocytology, andRT-PCR of tyrosine hydroxylase, GAGE, and MAGE

Background. We first explored the use of multiple molecular markers to over come tumor heterogeneity. Sixty-seven neuroblastoma (NB) tumors were tested far the expression of CAGE, MAGE-1, MAGE-2, MAGE-3, and MAGE-4 by RT-PCR a nd then chemiluminescence; 82% of tumors had delectable GAGE, and 88% expre ssed at least one of the four MAGE genes. Procedure and Results. By combini ng GAGE and MAGE, 64 of 67 (95%) of tumors became detectable; 17 of 67 coex pressed all five molecular markers. Neither GAGE nor MAGE expression correl ated with stage. GAGE was found to have the broadest (18 of 18) expression among stage 4 tumors. Two hundred fifty nine bone marrows from 99 patients were then studied for NB positivity by four detection methods: histology, i mmunocytology, and molecular detection by CAGE and tyrosine hydroxylase (TH ) mRNA. Two hundred seven samples were NB-positive by one detection method. All four techniques were comparable in detecting tumor cells at diagnosis and at relapse. CAGE and immunocytology were far more sensitive than histol ogy and TH mRNA when marrows were sampled during chemotherapy and at the ti me of clinical remission. Conclusions. By combining multiple molecular mark ers and independent screening techniques, we may be able to overcome tumor heterogeneity and expedite the detection of microscopic disease in the clin ical management of neuroblastoma. Med. Pediatr. Oncol. 36: 210-212, 2001. ( C) 2001 Wiley-Liss, Inc.