DEMONSTRATION OF APOPTOSIS IN NEUROBLASTOMA AND ITS RELATIONSHIP TO TUMOR-REGRESSION

The in vivo occurrence of apoptosis in neuroblastomas was investigated . Histologically, a number of tumour cells showed typical apoptotic ch anges, including cell shrinkage, condensed and fragmented nuclei, eosi nophilic cytoplasm, and absence of the inflammatory response. These ce lls coincided closely with the so-called karyorrhectic cells. An elect rophoretic DNA ladder, a functional hallmark of apoptosis, was demonst rated in four of six tumours, and DNA fragmentation was detected in si tu by terminal deoxytransferase-mediated nick end-labelling in 26 of 3 5 tumour specimens (74%). The labelled cell counts ranged from 5 to 62 per 5000 tumour cells (mean+/- SD: 15.0+/- 14.5). Immunoperoxidase st aining revealed that an apoptosis-suppressing protein, bcl-2, was expr essed abundantly in advanced-stage tumours, whereas it was absent from karyorrhectic-apoptotic cells. Several tumours with the potential for spontaneous regression were bcl-2-deficient. Immunostaining of the Fa s receptor for apoptosis demonstrated that the tumour cells expressed this molecule on their cell surfaces. Our results provide evidence of apoptosis in neuroblastomas and suggest that bcl-2 and the Fas recepto r may play a role in its regulatory mechanisms.