Blood vessel maturation in retinoblastoma tumors: spatial distribution of neovessels and mature vessels and its impact on ocular treatment

Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1020-4. doi: 10.1167/iovs.08-2654. Epub 2008 Oct 24.

Abstract

Purpose: The purposes of this study were to evaluate the spatial distribution of neovessels versus mature vessels in both human retinoblastoma (RB) and LH(BETA)T(AG) tumors, assess similarities and differences between the animal model and the human RB specimens, and determine whether vessel maturation is associated with risk factors for metastasis.

Methods: Immunohistochemical analyses were performed on human (n = 10) and LH(BETA)T(AG) (n = 11) enucleation specimens to evaluate the spatial distribution of neovessels and mature vessels. In human RB, vessel maturation was correlated with treatment history and metastatic risk factors.

Results: In human RB, the percentage of neovessels was higher in the periphery of the tumor than in the center (P = 0.021). This finding was mostly attributed to the distribution of large-caliber vessels (i.e., neovessels were higher in the periphery for large [P = 0.050]- and medium [P = 0.032]-caliber vessels; and mature vessels were higher in the center for large-caliber vessels [P = 0.032]). In this small series, vessel maturation did not correlate with risk for metastasis. Similar results were observed in LH(BETA)T(AG) tumors. The percentage of large-caliber neovessels was higher in the periphery than in the center (P = 0.038).

Conclusions: There is a spatially distributed, heterogeneous vessel population containing neovessels and mature vessels in advanced RB disease. There is a significantly higher concentration of mature, large-caliber vessels in the center of tumors that is similar in human RB and LH(BETA)T(AG) retinal tumors. From these data the authors hypothesize that tumor vessel maturation in RB initiates in central regions of the tumor and radiates toward the periphery.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antigens, CD / metabolism
  • Biomarkers / metabolism
  • Blood Vessels / pathology
  • Child, Preschool
  • Collagen Type IV / metabolism
  • Disease Models, Animal*
  • Endoglin
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Infant
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Receptors, Cell Surface / metabolism
  • Retinal Neoplasms / blood supply*
  • Retinal Neoplasms / metabolism
  • Retinal Neoplasms / pathology
  • Retinoblastoma / blood supply*
  • Retinoblastoma / metabolism
  • Retinoblastoma / pathology

Substances

  • Actins
  • Angiogenesis Inhibitors
  • Antigens, CD
  • Biomarkers
  • Collagen Type IV
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface