title: Relationship between histopathological features, MYCN amplification, and prognosis: a UKCCSG study. United Kingdom Children Cancer Study Group.
abstract: Histological sections from 231 patients with neuroblastoma were reviewed and morphological features and their relationship to age, stage, MYCN amplification (in 128 tumours by Southern analyses), and clinical outcome (based on Shimada risk grouping) determined. Stage 4 disease was associated with poorly differentiated and undifferentiated tumours (P = 0.001), an MKI of >2% (P< 0.001), and Shimada unfavourable histology (UHi) P< 0.0001. In univariate analysis MKI was significant in predicting a poorer relapse-free survival (RFS), low vs. intermediate and high (P< 0.001). Age, MYCN amplification, and Shimada UH also emerged as significant variables. There was a higher proportion of MYCN-amplified tumours with Shimada UH (P = 0.03), and this group had a decreased RFS (P = 0.002). In patients with Shimada FH, MYCN amplification did not significantly predict a poor prognosis. In those with stage 4 disease, Shimada classification was not significant in predicting survival (P = 0.97); the same was true for those over the age of 1 year (P = 0.66). In multivariate analysis, MYCN amplification and Shimada UH both emerged as independent prognostic factors. In conclusion, morphological features assigned some subsets of patients to prognostic risk groups. Most MYCN-amplified tumours have unfavourable histology and a poorer prognosis. However, in patients with stage 4 disease and those over the age of 1 year, other factors that may influence prognosis should be determined.
authors.affiliation: Cancer Research Unit, Medical School, University of Newcastle upon Tyne, United Kingdom.
authors.forename: R E
authors.initials: RE
authors.lastname: George
authors.forename: S
authors.initials: S
authors.lastname: Variend
authors.forename: C
authors.initials: C
authors.lastname: Cullinane
authors.forename: S J
authors.initials: SJ
authors.lastname: Cotterill
authors.forename: A G
authors.initials: AG
authors.lastname: McGuckin
authors.forename: C
authors.initials: C
authors.lastname: Ellershaw
authors.forename: J
authors.initials: J
authors.lastname: Lunec
authors.forename: A D
authors.initials: AD
authors.lastname: Pearson
mesh_terms: D000367:Age Factors; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D018305:Ganglioneuroblastoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007223:Infant; D015993:Life Tables; D008940:Mitotic Index; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D017154:Stromal Cells / Q000473:pathology; D016019:Survival Analysis; D006113:United Kingdom / Q000453:epidemiology