Oue T, Fukuzawa M, Kusafuka T, Kohmoto Y, Imura K, Nagahara S, Okada A
Department of Pediatric Surgery, Osaka University Medical School, Japan.
J Pediatr Surg. 1996 Feb;31(2):251-7. doi: 10.1016/s0022-3468(96)90009-3.
Spontaneous regression occurs in some cases of neuroblastoma, especially stage IVS. The incidence of neuroblastoma has been reported to be increasing since the mass screening program was introduced in Japan. This would indicate that the screening is detecting regressing tumors. However, the mechanism of regression is still unknown. To evaluate the hypothesis that the regression might be related to apoptosis, the authors examined apoptosis by in situ end-labeling of fragmented DNA and expression of the apoptosis-suppressing protein bcl-2.
One hundred eighteen neuroblastoma cases were available for examination. Eighty (67.8%) were detected by the mass screening program. Serial sections were cut from paraffin-embedded tumors. A modified TdT-mediated dUTP nick end-labeling (TUNEL) method was performed to detect apoptosis. Immunohistochemical analysis was performed to detect bcl-2 expression.
In cases under 1 year of age or with a favorable clinical stage, the incidence of apoptosis was significantly high. Expression of bcl-2 was associated with N-myc amplification and unfavorable histology (Shimada classification). Tumors in patients under 1 year of age often had areas where cellularity was markedly decreased, and apoptosis was often observed while bcl-2 expression was reduced. In such cases, there was a negative correlation between occurrence of apoptosis and bcl-2 expression. This suggests that apoptosis may be related to spontaneous regression in neuroblastoma.
神经母细胞瘤的某些病例会出现自发消退，尤其是IVS期。自日本引入大规模筛查计划以来，据报道神经母细胞瘤的发病率一直在上升。这表明筛查正在检测到正在消退的肿瘤。然而，消退的机制仍然未知。为了评估消退可能与细胞凋亡有关的假说，作者通过对断裂DNA进行原位末端标记和检测凋亡抑制蛋白bcl-2的表达来研究细胞凋亡。
有118例神经母细胞瘤病例可供检查。其中80例（67.8%）是通过大规模筛查计划检测到的。从石蜡包埋的肿瘤中切取连续切片。采用改良的TdT介导的dUTP缺口末端标记（TUNEL）法检测细胞凋亡。进行免疫组织化学分析以检测bcl-2的表达。
在1岁以下或临床分期良好的病例中，细胞凋亡的发生率显著较高。bcl-2的表达与N-myc扩增和不良组织学（岛田分类）有关。1岁以下患者的肿瘤通常有细胞明显减少的区域，经常观察到细胞凋亡，而bcl-2表达降低。在这些病例中，细胞凋亡的发生与bcl-2表达之间呈负相关。这表明细胞凋亡可能与神经母细胞瘤的自发消退有关。
