Koizumi H, Wakisaka M, Nakada K, Takakuwa T, Fujioka T, Yamate N, Uchikoshi T
Second Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan.
Virchows Arch. 1995;427(2):167-73. doi: 10.1007/BF00196522.
The in vivo occurrence of apoptosis in neuroblastomas was investigated. Histologically, a number of tumour cells showed typical apoptotic changes, including cell shrinkage, condensed and fragmented nuclei, eosinophilic cytoplasm, and absence of the inflammatory response. These cells coincided closely with the so-called karyorrhectic cells. An electrophoretic DNA ladder, a functional hallmark of apoptosis, was demonstrated in four of six tumours, and DNA fragmentation was detected in situ by terminal deoxytransferase-mediated nick end-labelling in 26 of 35 tumour specimens (74%). The labelled cell counts ranged from 5 to 62 per 5000 tumour cells (mean +/- SD: 15.0 +/- 14.5). Immunoperoxidase staining revealed that an apoptosis-suppressing protein, bcl-2, was expressed abundantly in advanced-stage tumours, whereas it was absent from karyorrhectic-apoptotic cells. Several tumours with the potential for spontaneous regression were bcl-2-deficient. Immunostaining of the Fas receptor for apoptosis demonstrated that the tumour cells expressed this molecule on their cell surfaces. Our results provide evidence of apoptosis in neuroblastomas and suggest that bcl-2 and the Fas receptor may play a role in its regulatory mechanisms.
研究了神经母细胞瘤体内凋亡的发生情况。组织学上，许多肿瘤细胞显示出典型的凋亡变化，包括细胞皱缩、核浓缩和碎片化、嗜酸性细胞质以及无炎症反应。这些细胞与所谓的核崩解细胞密切相符。凋亡的一个功能标志——电泳DNA梯带，在六个肿瘤中的四个中得到证实，并且通过末端脱氧核苷酸转移酶介导的缺口末端标记在35个肿瘤标本中的26个（74%）中检测到了DNA片段化。每5000个肿瘤细胞中标记细胞计数范围为5至62个（平均值±标准差：15.0±14.5）。免疫过氧化物酶染色显示，一种凋亡抑制蛋白bcl-2在晚期肿瘤中大量表达，而在核崩解凋亡细胞中不存在。几个具有自发消退潜力的肿瘤是bcl-2缺陷型的。对凋亡的Fas受体进行免疫染色表明，肿瘤细胞在其细胞表面表达该分子。我们的结果提供了神经母细胞瘤中凋亡的证据，并表明bcl-2和Fas受体可能在其调节机制中发挥作用。
