Differentiation, proliferation and apoptosis in primary and recurrent primitive neuroectodermal tumors of childhood

Primitive neuroectodermal tumors (PNETs) of the CNS are a group of embryona l tumors composed of small undifferentiated or poorly differentiated cells. Infratentorially located PNETs are a synonym for medulloblastomas. In this study 31 PNETs, including 5 recurrent tumors, were examined. All children underwent neurosurgery and chemotherapy according to the HIT and HIT-SKK pr otocols. The specimens were investigated both for their expression of nine immunohistochemical markers for neuronal, astrocytic, mesenchymal and epith elial differentiation and for their proliferation. Results regarding cellul ar differentiation were confirmed ultrastructurally Apoptosis was detected by labeling the 3'OH ends generated by DNA fragmentation and by electron mi croscopy. Glial differentiation was shown to have a prognostic relevance, w ith an elevated (twofold) risk of recurrence. Neuronal differentiation also indicated a tendency to poor prognosis. Those tumors that recurred later s howed an increased proliferation rate (69%) compared with nonrecurrent tumo rs (58%). Apoptosis was identified in all tumors examined. The proportion o f apoptotic cells could not be related to the effect of therapy. These resu lts indicate that cellular differentiation may be a useful predicative fact or for the prognosis of cerebral PNETs.