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

AbstractPURPOSE:
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.
AuthorsYolanda Piña, Hinda Boutrid, Amy Schefler, Sander Dubovy, William Feuer, Maria-Elena Jockovich, Timothy G Murray
JournalInvestigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 50 Issue 3 Pg. 1020-4 (Mar 2009) ISSN: 1552-5783 [Electronic] United States
PMID18952925 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Angiogenesis Inhibitors
  • Antigens, CD
  • Biomarkers
  • Collagen Type IV
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
Topics
  • 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, metabolism, pathology)
  • Receptors, Cell Surface (metabolism)
  • Retinal Neoplasms (blood supply, metabolism, pathology)
  • Retinoblastoma (blood supply, metabolism, pathology)

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