title: Extracellular matrix composition defines an ultra-high-risk group of neuroblastoma within the high-risk patient cohort.
abstract: Although survival for neuroblastoma patients has dramatically improved in recent years, a substantial number of children in the high-risk subgroup still die.
  
  
  
  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.
  
  
  
  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.
  
  
  
  We demonstrate that quantification of tumour stroma components by morphometric techniques has the potential to improve risk stratification of neuroblastoma patients.
authors.affiliation: Department of Pathology, Medical School, University of Valencia - INCLIVA, Avda. Blasco Ibañez 15, 46010 Valencia, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Tadeo
authors.affiliation: Department of Pathology, Medical School, University of Valencia - INCLIVA, Avda. Blasco Ibañez 15, 46010 Valencia, Spain.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Berbegall
authors.affiliation: Pediatric Oncology Unit, University and Polytechnic Hospital La Fe, Avda. Fernando Abril Martorell 106, 46026, Valencia, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Castel
authors.affiliation: Service of Pediatric Oncohematology, University Hospital La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: García-Miguel
authors.affiliation: Department of Pathology, Medical School, University of Valencia - INCLIVA, Avda. Blasco Ibañez 15, 46010 Valencia, Spain.
authors.forename: Robert
authors.initials: R
authors.lastname: Callaghan
authors.affiliation: Division of Molecular Medicine Medicon Village, Building 406 Lund University, SE-223 81 Lund, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Påhlman
authors.affiliation: Department of Pathology, Medical School, University of Valencia - INCLIVA, Avda. Blasco Ibañez 15, 46010 Valencia, Spain.
authors.forename: Samuel
authors.initials: S
authors.lastname: Navarro
authors.affiliation: Department of Pathology, Medical School, University of Valencia - INCLIVA, Avda. Blasco Ibañez 15, 46010 Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Noguera
mesh_terms: D001808:Blood Vessels / Q000473:pathology; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D009447:Neuroblastoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012155:Reticulin / Q000378:metabolism; D012306:Risk; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D024042:Collagen Type I; D006025:Glycosaminoglycans; D012155:Reticulin