title: Lack of immunocytological GD2 expression on neuroblastoma cells in bone marrow at diagnosis, during treatment, and at recurrence.
abstract: Loss of disialoganglioside 2 (GD2) expression in neuroblastoma (NB) bone marrow cells has been reported in rare cases. This study investigated prospectively the frequency and the patterns of visible GD2 loss at diagnosis, during treatment, and at recurrence.
  
  
  
  Bone marrow aspirates of patients with new or recurrent stage 4 and 4S NB diagnosed between January 1, 2002 and August 31, 2013 were investigated in parallel by cytology and GD2 immunocytology. Complete negative immunostaining was defined if staining was absent in all and partial if absent in a portion and/or in case of atypical faint staining.
  
  
  
  Of 1,261 investigated trial patients of all stages, 474 had unequivocal cytological bone marrow infiltration at initial diagnosis. Thirty-seven patients had tumor cells with complete or partial negative GD2 staining at initial diagnosis, nine during chemotherapy, and 11 at recurrence (altogether 12.0%). The percentage of GD2 negativity in stages 4 and 4S were similar (13% and 9%, respectively). Complete negativity was seen in 14 and partial in 43 cases. Twenty-one cases changed from positive to negative (15 to partial and six to complete) and three cases from negative to positive staining (two to partial and one to complete). The GD2 negative and positive groups were not different regarding tumor sites, molecular characteristics, histology, and tumor markers. Children with stage 4 and GD2 negativity tended to be older at diagnosis (42 vs. 32 months, P = 0.056). Event-free survival and overall survival comparing negative versus positive staining did not show any differences.
  
  
  
  Complete or partial lack of GD2 staining on NB cells in bone marrow is more frequent than currently recognized.
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Schumacher-Kuckelkorn
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Volland
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Gradehandt
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Simon
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D005732:Gangliosides; C019403:ganglioside, GD2
keywords: MRD; chemotherapy; clinical trials; immunotherapy; neuroblastoma biology; tumor markers