PHOX2B Is a Novel and Specific Marker for Minimal Residual Disease Testing in Neuroblastoma

被引:77
|
作者
Stutterheim, Janine
Gerritsen, Annemieke
Zappeij-Kannegieter, Lily
Kleijn, Ilona
Dee, Rob
Hooft, Lotty
van Noesel, Max M.
Bierings, Marc
Berthold, Frank
Versteeg, Rogier
Caron, Huib N.
van der Schoot, C. Ellen
Tytgat, Godelieve A. M.
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1105 AZ Amsterdam, Netherlands
[2] Sanquin AMC, Landsteiner Lab, Amsterdam, Netherlands
[3] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Pediat Oncol Hematol, Rotterdam, Netherlands
[4] Wilhelmina Childrens Hosp, Dept Pediat Hematol, Utrecht Med Ctr, Utrecht, Netherlands
[5] Univ Cologne, Dept Pediat Oncol & Hematol, Childrens Hosp, D-5000 Cologne 41, Germany
关键词
D O I
10.1200/JCO.2007.13.6531
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) in neuroblastoma can be used to monitor therapy response and to evaluate stem cell harvests. Commonly used PCR markers, tyrosine hydroxylase (TH) and GD2 synthase, have expression in normal tissues, thus limiting MRD detection. To identify a more specific MRD marker, we tested PHOX2B. 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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页码:5443 / 5449
页数:7
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