About 30% of neuroblastomas exhibit N-myc amplification. Neuroblastomas with Nmyc amplification tend to have a stroma-poor undifferentiated histopathologic phenotype and a high mitosis-karyorrhexis index (MKI). Karyorrhectic or pyknotic cells in neuroblastomas are closely related to apoptosis. Using fluorescence in situ hybridization (FISH) technique on formal in-fixed paraffin-embedded tissue, we conducted a retrospective study on 42 cases of neuroblastomas to investigate the relationship between N-myc amplification and 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 demonstrated N-myc amplification. After exclusion of nine tumors from patients who had prior chemotherapy, 3 3 tumors were available for thorough investigation. Based on the morphology of apoptotic cells, seven of the eight neuroblastomas with N-myc amplification had high apoptotic cell counts (more than 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.
