Extracellular matrix composition defines an ultra-high-risk group of neuroblastoma within the high-risk patient cohort

Br J Cancer. 2016 Aug 9;115(4):480-9. doi: 10.1038/bjc.2016.210. Epub 2016 Jul 14.

Abstract

Background: Although survival for neuroblastoma patients has dramatically improved in recent years, a substantial number of children in the high-risk subgroup still die.

Methods: We aimed to define a subgroup of ultra-high-risk patients from within the high-risk cohort. We used advanced morphometric approaches to quantify and characterise blood vessels, reticulin fibre networks, collagen type I bundles, elastic fibres and glycosaminoglycans in 102 high-risk neuroblastomas specimens. The Kaplan-Meier method was used to correlate the analysed elements with survival.

Results: The organisation of blood vessels and reticulin fibres in neuroblastic tumours defined an ultra-high-risk patient subgroup with 5-year survival rate <15%. Specifically, tumours with irregularly shaped blood vessels, large sinusoid-like vessels, smaller and tortuous venules and arterioles and with large areas of reticulin fibres forming large, crosslinking, branching and haphazardly arranged networks were linked to the ultra-high-risk phenotype.

Conclusions: We demonstrate that quantification of tumour stroma components by morphometric techniques has the potential to improve risk stratification of neuroblastoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Vessels / pathology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Collagen Type I / metabolism
  • Elastic Tissue / metabolism
  • Elastic Tissue / pathology
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Glycosaminoglycans / metabolism
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Neuroblastoma / metabolism
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology*
  • Prognosis
  • Reticulin / metabolism
  • Risk
  • Risk Assessment
  • Survival Rate

Substances

  • Collagen Type I
  • Glycosaminoglycans
  • Reticulin