title: Correlation of MYCN amplification, Trk-A and CD44 expression with clinical stage in 250 patients with neuroblastoma.
abstract: In contrast to MYCN amplification, expression of either trk-A or CD44 in neuroblastoma is a favourable prognostic factor and were therefore investigated in tumours from 250 patients. One hundred and eleven localised/4s (Group 1) and 139 stage 4 (Group 2) tumours were analysed. MYCN copy number was obtained by Southern blotting or PCR amplification and was detected in 28 stage 4 tumours. Trk-A and CD44 expression was detected by immunoperoxidase staining using murine monoclonal antibodies 5C3 and L178, respectively. Expression was scored as positive (homogeneous), mixed (heterogeneous) or non-reactive (negative). Trk-A expression was found in 95% of Group 1 tumours and 49% of Group 2 tumours. CD44 expression was found in 100% of Group 1 tumours, the majority of which had a strong homogeneous expression. Lack of CD44 expression occurred in 25% of tumours, all stage 4 neuroblastoma. Of the 28 MYCN amplified tumours, 27/28 (96%) were trk-A negative, and 13/28 (46%) CD44 negative. We conclude that (1) a significant percentage of stage 4 neuroblastoma express either or both trk-A and CD44, (2) the absence of CD44 expression is highly restricted to stage 4 neuroblastoma and is associated with the lack of trk-A expression, (3) trk-A negativity among CD44-positive tumours is associated with stage 4 neuroblastoma and (4) the absence of trk-A expression is highly correlated with MYCN amplification.
authors.affiliation: Department of Pediatrics and Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kramer
authors.forename: N K
authors.initials: NK
authors.lastname: Cheung
authors.forename: W L
authors.initials: WL
authors.lastname: Gerald
authors.forename: M
authors.initials: M
authors.lastname: LaQuaglia
authors.forename: B H
authors.initials: BH
authors.lastname: Kushner
authors.forename: J M
authors.initials: JM
authors.lastname: LeClerc
authors.forename: L
authors.initials: L
authors.lastname: LeSauter
authors.forename: H U
authors.initials: HU
authors.lastname: Saragovi
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002675:Child, Preschool; D018572:Disease-Free Survival; D005729:Ganglioneuroma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007223:Infant; D008565:Membrane Proteins / Q000378:metabolism*; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020917:Receptor, trkA
chemical_list: D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D020917:Receptor, trkA