Absence of polysialylated NCAM is an unfavorable prognostic phenotype for advanced stage neuroblastoma.
BACKGROUND
The expression of a neural crest stem cell marker, polysialic acid (polySia), and its main carrier, neural cell adhesion molecule (NCAM), have been detected in some malignant tumors with high metastatic activity and unfavorable prognosis, but the diagnostic and prognostic value of polySia-NCAM in neuroblastoma is unclear.


METHODS
A tumor tissue microarray (TMA) of 36 paraffin-embedded neuroblastoma samples was utilized to detect polySia-NCAM expression with a polySia-binding fluorescent fusion protein, and polySia-NCAM expression was compared with clinical stage, age, MYCN amplification status, histology (INPC), and proliferation index (PI).


RESULTS
PolySia-NCAM-positive neuroblastoma patients had more often metastases at diagnosis, and polySia-NCAM expression associated with advanced disease (P = 0.047). Most interestingly, absence of polySia-NCAM-expressing tumor cells in TMA samples, however, was a strong unfavorable prognostic factor for overall survival in advanced disease (P = 0.0004), especially when MYCN was not amplified. PolySia-NCAM-expressing bone marrow metastases were easily detected in smears, aspirates and biopsies.


CONCLUSIONS
PolySia-NCAM appears to be a new clinically significant molecular marker in neuroblastoma, hopefully with additional value in neuroblastoma risk stratification.
Korja
Miikka
M
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland. mkorja@utu.fi
Jokilammi
Anne
A
Salmi
Toivo T
TT
Kalimo
Hannu
H
Pelliniemi
Tarja-Terttu
TT
Isola
Jorma
J
Rantala
Immo
I
Haapasalo
Hannu
H
Finne
Jukka
J
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D006801:Humans; D046228:Microarray Analysis; D000071447:N-Myc Proto-Oncogene Protein; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D019006:Neural Cell Adhesion Molecules; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012794:Sialic Acids; C021319:polysialic acid