Detection of microscopic neuroblastoma in marrow by histology, immunocytology, and reverse transcription-PCR of multiple molecular markers Journal Article


Authors: Cheung, I. Y.; Barber, D.; Cheung, N. K. V.
Article Title: Detection of microscopic neuroblastoma in marrow by histology, immunocytology, and reverse transcription-PCR of multiple molecular markers
Abstract: We explored the use of multiple molecular markers to overcome tumor heterogeneity. Sixty-seven neuroblastoma (NB) tumors were tested for the expression of GAGE, MAGE-1, MAGE-2, MAGE-3, and MAGE-4 by reverse transcription-PCR. Eighty-two percent of 67 NB tumors had detectable GAGE, and 88% expressed at least one of the four MAGE genes. By combining GAGE and MAGE, we found that 64 of 67 (95%) of tumors became detectable and 17 of 67 coexpressed all five molecular markers. Neither GAGE nor MAGE expression correlated with stage. GAGE was found to have the broadest (18 of 18) expression among stage 4 tumors. A total of 259 bone marrows from 99 patients were then studied for NB positivity by four detection methods: histology (aspirate by Wright-Giemsa and biopsy by H and E staining), immunocytology (by a panel of anti-G(D2) monoclonal antibodies), and molecular detection by GAGE and tyrosine hydroxylase mRNA. Two hundred seven samples were NB positive by one or more detection methods. All four techniques were comparable in detecting tumor cells at diagnosis. GAGE and immunocytology were more sensitive than histology or tyrosine hydroxylase reverse transcription-PCR when marrows were obtained from patients on therapy or off therapy during clinical remission. Agreement among tests was highest at the time of gross disease. We conclude that, by combining multiple molecular markers and independent screening techniques, we may be able to overcome tumor heterogeneity and expedite the detection of microscopic disease in the clinical management of NB.
Keywords: immunohistochemistry; controlled study; human tissue; major clinical study; neoplasm staging; reproducibility of results; reverse transcription polymerase chain reaction; gene expression; bone marrow; neoplasm proteins; tumor markers, biological; tumor cells, cultured; tumor marker; histology; cell heterogeneity; antigens, neoplasm; neuroblastoma; messenger rna; tyrosine 3 monooxygenase; immunocytochemistry; reverse transcriptase polymerase chain reaction; bone marrow neoplasms; bone marrow metastasis; tyrosine 3-monooxygenase; humans; human; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 4
Issue: 11
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 1998-11-01
Start Page: 2801
End Page: 2805
Language: English
PUBMED: 9829745
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Nai-Kong Cheung
    648 Cheung
  2. Irene Y Cheung
    96 Cheung
  3. Dianna   Barber
    1 Barber