Ikeda H, Hirato J, Akami M, Matsuyama S, Suzuki N, Takahashi A, Kuroiwa M
Department of Surgery, Gunma Children's Medical Center, Japan.
J Pediatr Surg. 1995 Jun;30(6):805-8. doi: 10.1016/0022-3468(95)90752-1.
Bcl-2 protooncogene, originally discovered at the chromosomal breakpoint of the t(14;18) in follicular lymphoma, is known to regulate the process of programmed cell death or apoptosis. The inhibition of apoptosis is thought to be one of the mechanisms involved in the development of tumors. To investigate the possible association of bcl-2 protooncogene with the tumorigenesis of neuroblastomas, the authors examined bcl-2 expression by immunohistochemistry in 49 neuroblastomas and 7 ganglioneuromas. The distribution of apoptotic cells was also examined by the TUNEL method (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Bcl-2 oncoprotein was detected in the cytoplasm in 40 of 49 neuroblastomas (81.6%). There was no correlation between bcl-2 oncoprotein expression and the clinical features of neuroblastoma. The incidence of bcl-2-positive tumors in ganglioneuroma was significantly lower than that in neuroblastoma (28.6%) (P < .01). TUNEL stained the nuclei of tumor cells in 11 of 34 (32.4%) neuroblastomas. TUNEL-positive cells tended to be located around calcifications in neuroblastomas in patients less than 1 year old. Examination of serial sections showed that apoptotic cells were distributed in the area where bcl-2 oncoprotein was not expressed. What we have observed indicates that apoptosis of neuroblastoma cells may be regulated by bcl-2 expression. Our observations suggest that the survival of neuroblastoma cells might be promoted by bcl-2 expression and that bcl-2 might be associated with the tumorigenesis of neuroblastomas.
Bcl-2原癌基因最初是在滤泡性淋巴瘤的t(14;18)染色体断点处发现的，已知其可调节程序性细胞死亡或凋亡过程。凋亡抑制被认为是肿瘤发生所涉及的机制之一。为了研究bcl-2原癌基因与神经母细胞瘤肿瘤发生的可能关联，作者采用免疫组织化学方法检测了49例神经母细胞瘤和7例神经节神经瘤中的bcl-2表达。还通过TUNEL法（末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法）检测了凋亡细胞的分布。在49例神经母细胞瘤中的40例（81.6%）的细胞质中检测到了Bcl-2癌蛋白。bcl-2癌蛋白表达与神经母细胞瘤的临床特征之间无相关性。神经节神经瘤中bcl-2阳性肿瘤的发生率显著低于神经母细胞瘤（28.6%）（P <.01）。在34例神经母细胞瘤中的11例（32.4%）中，TUNEL法染出了肿瘤细胞核。在小于1岁的神经母细胞瘤患者中，TUNEL阳性细胞倾向于位于钙化灶周围。连续切片检查显示，凋亡细胞分布在未表达bcl-2癌蛋白的区域。我们的观察结果表明，神经母细胞瘤细胞的凋亡可能受bcl-2表达的调节。我们的观察结果提示，bcl-2表达可能促进神经母细胞瘤细胞的存活，并且bcl-2可能与神经母细胞瘤的肿瘤发生有关。
