Abstract | PURPOSE: PATIENTS AND METHODS: To determine PHOX2B, TH, and GD2 synthase expression in normal tissues, it was measured by real-time quantitative PCR in samples of normal bone marrow (BM; n = 51), peripheral blood (PB; n = 37), and peripheral-blood stem cells (PBSCs; n = 24). Then, 289 samples of 101 Dutch patients and 47 samples of 43 German patients were tested for PHOX2B and TH; these samples included 52 tumor, 214 BM, 32 BM, and 38 PBSC harvests. Of the 214 BM samples, 167 were compared with cytology, and 47 BM samples were compared with immunocytology (IC). RESULTS: In contrast to TH and GD2 synthase, PHOX2B was not expressed in any of the normal samples. In patient samples, PHOX2B was detected in 32% cytology-negative and in 14% IC-negative samples and in 94% of cytology-positive and in 90% of IC-positive BM samples. Overall, PHOX2B was positive in 43% compared with 31% for TH. In 24% of all samples, TH expression was inconclusive, which is similar to expression found in normal tissues. In 42% of these samples, PHOX2B expression was positive. CONCLUSION: PHOX2B is superior to TH and GD2 synthase in specificity and sensitivity for MRD detection of neuroblastoma by using real-time quantitative PCR. We propose to include PHOX2B in additional prospective MRD studies in neuroblastoma alongside TH and other MRD markers.
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Authors | Janine Stutterheim, Annemieke Gerritsen, Lily Zappeij-Kannegieter, Ilona Kleijn, Rob Dee, Lotty Hooft, Max M van Noesel, Marc Bierings, Frank Berthold, Rogier Versteeg, Huib N Caron, C Ellen van der Schoot, Godelieve A M Tytgat |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 26
Issue 33
Pg. 5443-9
(Nov 20 2008)
ISSN: 1527-7755 [Electronic] United States |
PMID | 18838715
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- Homeodomain Proteins
- NBPhox protein
- Nerve Tissue Proteins
- Transcription Factors
- Tyrosine 3-Monooxygenase
- N-Acetylgalactosaminyltransferases
- (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
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Topics |
- Adolescent
- Biomarkers, Tumor
(analysis)
- Bone Marrow
(chemistry)
- Child
- Child, Preschool
- Female
- Homeodomain Proteins
(analysis)
- Humans
- Infant
- Male
- N-Acetylgalactosaminyltransferases
- Neoplasm, Residual
- Nerve Tissue Proteins
(analysis)
- Neuroblastoma
(diagnosis, pathology)
- Polymerase Chain Reaction
- Sensitivity and Specificity
- Transcription Factors
(analysis)
- Tyrosine 3-Monooxygenase
(analysis)
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