Detection of neuroblastoma cells in bone marrow and peripheral blood by different techniques: accuracy and relationship with clinical features of patients.
OBJECTIVE
Detection of metastatic tumor cells in bone marrow (BM) and peripheral blood (PB) of children with neuroblastoma is crucial for prognosis and planning of therapy. Aims of this large descriptive repeated survey were to evaluate the diagnostic accuracy of different techniques in diagnostic samples obtained at several disease course time points and to correlate positive results with patient clinical features and outcome.


METHODS
BM aspirates, trephine biopsies, PB, and peripheral blood stem cell (PBSC) samples from Italian children with neuroblastoma were analyzed by morphological and histologic techniques, as well as by immunocytochemistry (IC) for disialoganglioside GD(2) and reverse transcription-PCRs (RT-PCRs) for tyrosine hydroxylase (TH) and pgp9.5 genes. The diagnostic odd ratio (DOR) was used to measure the accuracy of the different techniques.


RESULTS
A total of 2,247 evaluations were done on 561 BM, 265 PB, and 69 PBSC samples from 247 patients. IC showed the best accuracy. Whereas TH RT-PCR accuracy was satisfactory, that of pgp9.5 was very low. Positive results obtained by IC in BM and PB samples at diagnosis from stage 1, 2, and 3 patients correlated with unfavourable outcome. No correlation was found between positive results obtained by IC or TH RT-PCR in BM, PB, and PBSC samples from stage 4 patients and their outcome.


CONCLUSIONS
Because of its elevated diagnostic accuracy, IC may represent a useful adjunct to conventional morphological techniques, especially in view of its potential prognostic role in patients with localized disease. Longitudinal multicenter studies are warranted to definitely establish the clinical usefulness of TH RT-PCR.
Corrias
Maria Valeria
MV
Laboratory of Oncology, Service of Epidemiology and Biostatistics, Department of Hematology-Oncology, and Service of Pathology, Istituto Gaslini, L.go Gaslini, 5, 16148 Genoa, Italy. mariavaleriacorrias@ospedale-gaslini,ge,it
Faulkner
Lawrence B
LB
Pistorio
Angela
A
Rosanda
Cristina
C
Callea
Francesco
F
Piccolo
Maria Serena Lo
MS
Scaruffi
Paola
P
Marchi
Cinzia
C
Lacitignola
Laura
L
Occhino
Marzia
M
Gambini
Claudio
C
Tonini
Gian Paolo
GP
Haupt
Riccardo
R
De Bernardi
Bruno
B
Pistoia
Vito
V
Garaventa
Alberto
A
D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology*; D001855:Bone Marrow Diseases / Q000097:blood / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D007223:Infant; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000097:blood / Q000175:diagnosis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism
D005732:Gangliosides; D012333:RNA, Messenger; C482860:UCHL1 protein, human; C025447:sialogangliosides; D014446:Tyrosine 3-Monooxygenase; D043222:Ubiquitin Thiolesterase