Quantitative analysis of proliferation, apoptosis, and angiogenesis in retinoblastoma and their association with the clinicopathologic parameters

Jpn J Ophthalmol. 2003 Nov-Dec;47(6):565-71. doi: 10.1016/j.jjo.2003.09.002.


Purpose: Quantitative analyses of proliferation, apoptosis, and angiogenesis, which may be important for the prognosis of retinoblastoma, were performed and possible associations with some well-known clinicopathologic parameters were investigated.

Methods: Fifty-three pathology specimens (43 enucleations, 10 exenterations) were evaluated by immunohistochemical methods. The proliferative index was detected by Ki67 antibody staining. The apoptotic index was calculated by the in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and angiogenesis was detected by CD34 antibody staining.

Results: The mean proliferative index was 37.63+/-11.12, the mean apoptotic index was 2.67+/-1.18, and the microvessel density and mean vascular area were determined as 3.14+/-1.4 and 38.73+/-12.70, respectively. Statistical analysis showed that the proliferative index was directly proportional to the tumor dimensions (P=.001). In addition, the tumor dimensions were larger in cases where the apoptotic index was below 2.4% (P=.011). In cases where the apoptotic index was over 2.4%, no metastasis was observed and also a lower proliferative index was found (P=.014).

Conclusions: Proliferation appears to be more important than apoptosis and angiogenesis in determining the tumor dimensions. The apoptotic index may be an important predictor of metastasis, and may be useful in the follow-up of bilateral cases with 1 eye enucleated.

MeSH terms

  • Apoptosis*
  • Cell Division
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Neovascularization, Pathologic*
  • Retinal Neoplasms / blood supply*
  • Retinal Neoplasms / pathology*
  • Retinal Neoplasms / physiopathology
  • Retinoblastoma / blood supply*
  • Retinoblastoma / pathology*
  • Retinoblastoma / physiopathology