Biological diagnosis for neuroblastoma using the combination of highly sensitive analysis of prognostic factors.
OBJECTIVE
To select the optimal treatment according to the degree of malignancy of neuroblastoma, it is essential to accurately and rapidly identify any genetic abnormalities associated with the prognosis. This study aims to assess the correlation between the combination of prognostic factors and the biologic findings of neuroblastoma using a highly sensitive analysis of prognostic factors.


METHODS
In 44 neuroblastoma primary samples, we determined the gene dosages of MYCN and Survivin (as the target of 17q gain) and the expression levels of MYCN, Survivin, and BIN1 using highly sensitive analysis (the quantitative polymerase chain reaction method); furthermore, we assessed the correlation between the combination of their prognostic factors and the biology of neuroblastoma.


RESULTS
The gene dosage of MYCN or Survivin was significantly associated with all known prognostic factors. The expression level of MYCN or Survivin was not significantly associated with any prognostic factors, whereas the expression level of BIN1 was significantly associated with 5 of 6 prognostic factors. Regarding the combination of MYCN amplification and 17q gain (the gene dosage of Survivin), and the low expression of BIN1, the rates of advanced stages (stage III or IV) were 100% for the cases with 3 factors, 63% for the cases with 2 factors, 42% for the cases with 1 factor, and 0% for the cases with null factor. Furthermore, the survival rates were 20% for the cases with 3 factors, 50% for the cases with 2 factors, 100% for the cases with 1 factor, and 100% for the cases with null factor.


CONCLUSIONS
The combination of gene dosages of MYCN and Survivin and the expression level of BIN1 using the quantitative polymerase chain reaction method was significantly correlated with the clinical stage and the patients' outcome. This combination of biologic factors may enhance the accuracy to the conventional criteria, but this would have to be shown in a much larger study that is adequately powered to detect such an advantage.
Tajiri
Tatsuro
T
Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. taji@pedsurg.med.kyusyu-u.ac.jp
Tanaka
Shinji
S
Higashi
Mayumi
M
Kinoshita
Yoshiaki
Y
Takahashi
Yukiko
Y
Tatsuta
Kyosuke
K
Suita
Sachiyo
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D000077022:Survivin; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; C107489:BIRC5 protein, human; D005819:Genetic Markers; D051034:Inhibitor of Apoptosis Proteins; C459801:MYCN protein, human; D008869:Microtubule-Associated Proteins; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000077022:Survivin; D025521:Tumor Suppressor Proteins