Hoehner J C, Hedborg F, Wiklund H J, Olsen L, Påhlman S
Department of Pathology, Uppsala University Hospital, Sweden.
Int J Cancer. 1995 Jul 4;62(1):19-24. doi: 10.1002/ijc.2910620106.
Apoptosis is the selective physiologic deletion of cells that are no longer required. Over-expression of the bcl-2 proto-oncogene extends survival of neurons otherwise destined for apoptosis. The unique capacity of neuroblastoma (NB) to undergo spontaneous regression and the prognostic dichotomy of children with this malignancy led us to evaluate bcl-2 expression and apoptosis in NB. An in situ DNA nick-labeling technique to detect apoptotic cells, as well as immunohistochemistry and morphology, were utilized in a selection of NB tumor specimens and in the human fetal sympathetic nervous system. bcl-2 expression was present in all 28 NB tumors examined and in sympathetic ganglia of the human fetus. Measurement of overall bcl-2 expression and of extent of apoptosis correlated with favorable prognosis. In low-stage tumors, bcl-2 expression was most intense in poorly differentiated tumor cells adjacent to fibrovascular stroma. Cells distant from the stroma exhibited increasing degrees of chromaffin differentiation, with apoptosis most evident in bcl-2-negative neuroblasts adjacent to well-differentiated NB cells. The spatial distribution of bcl-2 expression, apoptosis and chromaffin differentiation in favorable-prognosis NB may provide insight into mechanisms of persistent tumor existence or regression.
细胞凋亡是对不再需要的细胞进行的生理性选择性清除。bcl-2原癌基因的过度表达可延长原本注定要发生凋亡的神经元的存活时间。神经母细胞瘤（NB）具有自发消退的独特能力以及患有这种恶性肿瘤的儿童的预后二分法，这促使我们评估NB中的bcl-2表达和细胞凋亡情况。在一系列NB肿瘤标本以及人类胎儿交感神经系统中，采用了一种用于检测凋亡细胞的原位DNA缺口标记技术以及免疫组织化学和形态学方法。在所检测的所有28例NB肿瘤以及人类胎儿的交感神经节中均存在bcl-2表达。总体bcl-2表达的测量以及细胞凋亡程度与良好预后相关。在低分期肿瘤中，bcl-2表达在紧邻纤维血管基质的低分化肿瘤细胞中最为强烈。远离基质的细胞表现出嗜铬分化程度增加，凋亡在紧邻高分化NB细胞的bcl-2阴性成神经细胞中最为明显。预后良好的NB中bcl-2表达、细胞凋亡和嗜铬分化的空间分布可能为深入了解肿瘤持续存在或消退的机制提供线索。
