Diagnostic and prognostic markers in infants with disseminated neuroblastoma: a retrospective analysis from the Italian Cooperative Group for Neuroblastoma.
BACKGROUND
One fourth of infants with disseminated neuroblastoma experience unfavorable outcome. Treatment strategies vary and are based on clinical characteristics at diagnosis which lead to the definition of stage 4 or 4s. To identify the distribution and effect of different prognostic factors, a series of such infants diagnosed in Italy between 1991-1999 was reviewed.


METHODS
Data were retrospectively retrieved from the Italian Neuroblastoma Registry. One hundred infants, 32 stage 4 and 68 stage 4s, were eligible. Clinical and biological characteristics evaluated at diagnosis for their impact on survival were demographics, primary site, urinary excretion of vanillylmandelic and homovanillic acids, serum neuron specific enolase, LDH, and ferritin together with analysis for MYCN gene, DNA index, and 1p36 chromosome.


RESULTS
Stage 4 prevailed in the second six months of life and stage 4s in the first six months. Events were distributed over two years in stage 4, but occurred very early in stage 4s patients. Survival was respectively 72% and 77.9%. Unfavorable factors were MYCN amplification for both stages, elevated NSE and LDH and normal VMA for stage 4, and di-tetraploid DNA for stage 4s.


CONCLUSIONS
The frequency of stage 4s was greater than stage 4. MYCN amplification was the most unfavorable prognostic factor. Survival was similar to previous series, confirming that a part of such infants cannot be cured by current therapies.
Di Cataldo
Andrea
A
Department of Pediatric Hematology and Oncology, University of Catania, Catania, Italy. adicata@unict.it
Dau
Daniela
D
Conte
Massimo
M
Parodi
Stefano
S
De Bernardi
Bruno
B
Giuliano
Maria
M
Pession
Andrea
A
Viscardi
Elisabetta
E
Luksch
Roberto
R
Castellano
Aurora
A
Bertuna
Gregoria
G
Haupt
Riccardo
R
D015415:Biomarkers / Q000032:analysis*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005293:Ferritins / Q000032:analysis; D005819:Genetic Markers / Q000235:genetics*; D006719:Homovanillic Acid / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D000071447:N-Myc Proto-Oncogene Protein; D009362:Neoplasm Metastasis / Q000175:diagnosis; D009367:Neoplasm Staging / Q000379:methods*; D009447:Neuroblastoma / Q000175:diagnosis*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014642:Vanilmandelic Acid / Q000652:urine
D015415:Biomarkers; D005819:Genetic Markers; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D014642:Vanilmandelic Acid; D005293:Ferritins; D007770:L-Lactate Dehydrogenase; D010751:Phosphopyruvate Hydratase; D006719:Homovanillic Acid