The balance between proliferation and cell death is the major determinant o
f tumour growth. We analysed the proliferative and apoptotic indices (PI an
d AI, respectively) of 33 children with retinoblastoma. PI and AI were asse
ssed by immunohistochemistry for Ki-67 antigen and TUNEL staining, respecti
vely. The mean PI was 21.0+/-21.1%, and higher PI was associated with more
advanced tumour stage (P<0.0001) and poor clinical outcome (P<0.05). Patien
ts in whom amplified N-myc oncogene was found (n=6) determined by the multi
plex polymerase chain reaction tended to have a higher PI (37.6+/-27.2%) th
an those without amplified N-myc (n=27; PI=17.3+/-18.1). A PI value of over
40% was clearly associated with an unfavourable prognosis. The AI, however
, did not correlate with any of the other variables analysed. The findings
suggest that proliferation, but not apoptosis, is of critical significance
in retinoblastoma biology. PI, as determined by the Ki-67 antigen labelling
index, seems to be a relevant histopathological parameter that can predict
the clinical outcome of retinoblastoma.