About 30% of neuroblastomas exhibit N-myc amplification. Neuroblastomas wit
h N-myc amplification tend to have a stroma-poor undifferentiated histopath
ologic phenotype and a high mitosis-karyorrhexis index (MKI). Karyorrhectic
or pyknotic cells in neuroblastomas are closely related to apoptosis. Usin
g fluorescence in situ hybridization (FISK) technique on formalin-fixed par
affin-embedded tissue, we conducted a retrospective study on 42 cases of ne
uroblastomas to investigate the relationship between N-myc amplification an
d apoptosis. The identification of apoptotic cells was based on morphology
and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate
(UTP)-biotin nick end labeling (TUNEL) method. Eleven (26%) of 42 tumors de
monstrated N-myc amplification. After exclusion of nine tumors from patient
s who had prior chemotherapy, 33 tumors were available for thorough investi
gation. Based on the morphology of apoptotic cells, seven of the eight neur
oblastomas with N-myc amplification had high apoptotic cell counts (more th
an 200 per 5,000 tumor cells), whereas only three of the 25 tumors without
N-myc amplification revealed high apoptotic cells. Our results suggest that
N-myc amplification can be readily detected in routinely processed tissue
sections by FISH technique. Its presence has prognostic value and tends to
be associated with a high number of apoptotic cells in neuroblastomas.