INTERLEUKIN-1-BETA CONVERTING-ENZYME (ICE) IS PREFERENTIALLY EXPRESSED IN NEUROBLASTOMAS WITH FAVORABLE PROGNOSIS

To determine whether interleukin-1 beta converting enzyme (ICE) plays a role in the programmed cell death of neuroblastoma, we studied ICE e xpression in primary tumours. In patients in stages I, II and IVS, ICE mRNA was detected in 22 of 32 (69%) tumours, while only 5 of 26 (19%) tumours expressed ICE in stages III and IV (P<0.001). ICE mRNA was ex pressed in 27 of 47 (57%) tumours without MYCN amplification, but it w as not detected in any tumours with MYCN amplification (P<0.01). Immun ohistochemically, the cytoplasm was stained in all 15 neuroblastomas e xamined. The nuclei were stained in 12 neuroblastomas without MYCN amp lification, whereas only 1 of 3 tumours with MYCN amplification had po sitive staining in the nuclei. In ganglioneuromas, high levels of ICE mRNA were expressed, but immunostaining showed that the protease expre ssion was confined to the cytoplasm. These observations suggest that I CE may be associated with the spontaneous regression often seen in fav ourable neuroblastomas and that localisation of ICE protease in the ce ll may be important for the cell death pathway. Double staining for IC E and TUNEL showed that they were co-localised in some nuclei, but the distribution of ICE protease expression was not necessarily the same as that of DNA fragmentation, suggesting that the protease expression probably preceded DNA fragmentation during the apoptotic process. ICE may play an important role in regulating the apoptotic process of neur oblastoma. (C) 1997 Elsevier Science Ltd.