title: Absence of polysialylated NCAM is an unfavorable prognostic phenotype for advanced stage neuroblastoma.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland. mkorja@utu.fi
authors.forename: Miikka
authors.initials: M
authors.lastname: Korja
authors.forename: Anne
authors.initials: A
authors.lastname: Jokilammi
authors.forename: Toivo T
authors.initials: TT
authors.lastname: Salmi
authors.forename: Hannu
authors.initials: H
authors.lastname: Kalimo
authors.forename: Tarja-Terttu
authors.initials: TT
authors.lastname: Pelliniemi
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
authors.forename: Immo
authors.initials: I
authors.lastname: Rantala
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.forename: Jukka
authors.initials: J
authors.lastname: Finne
mesh_terms: 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*
chemical_list: 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