PHOX2B immunolabeling: a novel tool for the diagnosis of undifferentiated neuroblastomas among childhood small round blue-cell tumors.
Peripheral neuroblastic tumors are the most commonly occurring extracranial tumors in children. Although a reliable diagnosis is achievable in the majority of cases, diagnosis of a minority of peripheral neuroblastic tumor cases (especially undifferentiated neuroblastoma) poses a challenge compared with that of other pediatric small round blue-cell tumors. A panel of immunohistochemical markers and fusion transcripts is available for the diagnosis of such tumors, but the markers for neuroblastoma lack specificity and sensitivity. As the transcription factor PHOX2B is highly specific for the peripheral autonomic nervous system from which peripheral neuroblastic tumors are derived, we have assessed PHOX2B immunolabeling as a diagnostic tool in pediatric small round blue-cell tumors. We observed PHOX2B expression in all peripheral neuroblastic tumors, paragangliomas, and pheochromocytomas tested but in no other pediatric tumors among the 388 cases studied by expression microarray and the 109 cases studied by immunohistochemical analysis. We then assessed the results of PHOX2B immunohistochemistry in 12 cases of undifferentiated pediatric neoplasms: PHOX2B was expressed in 6/6 undifferentiated neuroblastomas and in no other small round blue-cell tumors. Finally, we showed that PHOX2B immunohistochemical analysis improves the diagnosis of undifferentiated neuroblastoma with high specificity and sensitivity.
APHP, Hôpital Robert Debré, Service de Pathologie, Paris, France.
Franck
F
Bielle
Paul
P
Fréneaux
Corinne
C
Jeanne-Pasquier
Aurélie
A
Maran-Gonzalez
Audrey
A
Rousseau
Laurence
L
Lamant
Régine
R
Paris
Gaëlle
G
Pierron
André Victor
AV
Nicolas
Xavier
X
Sastre-Garau
Olivier
O
Delattre
Franck
F
Bourdeaut
Michel
M
Peuchmaur
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D055028:Comparative Genomic Hybridization; D003584:Cytological Techniques; D018305:Ganglioneuroblastoma / Q000175:diagnosis; D005729:Ganglioneuroma / Q000175:diagnosis; D018398:Homeodomain Proteins / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D009447:Neuroblastoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000032:analysis* / Q000096:biosynthesis; D055815:Young Adult
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C109220:NBPhox protein; D012333:RNA, Messenger; D014157:Transcription Factors