The relationship of N-myc amplification and apoptosis in neuroblastoma

About 30% of neuroblastomas exhibit N-myc amplification. Neuroblastomas with N-myc 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 (FISK) technique on formalin-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, 33 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.