Pession A, Trerè D, Perri P, Rondelli R, Montanaro L, Mantovani W, Derenzini M, Paolucci G
Dipartimento di Patologia Sperimentale, Università di Bologna, Italy.
J Pathol. 1997 Nov;183(3):339-44. doi: 10.1002/(SICI)1096-9896(199711)183:3<339::AID-PATH935>3.0.CO;2-T.
In neuroblastoma, N-myc amplification has been found to be strikingly associated with rapid tumour progression and poor prognosis. Recent studies have demonstrated that cell proliferative activity also significantly predicts the clinical outcome in patients with neuroblastoma. In order to define the correlation between N-myc amplification and cell proliferation rate, in the present investigation the two parameters were first assessed in 48 neuroblastoma tumours. N-myc amplification was evaluated in frozen specimens by Southern-blot analysis using the NB 19-21 probe and it was detected in nine patients. Cell proliferative activity was determined by measuring the AgNOR protein area in histological sections selectively stained by silver. The mean AgNOR protein area value of neuroblastomas with N-myc amplification (3.63 +/- 1.62 microns2) was not significantly different from that of neuroblastomas without N-myc amplification (2.46 +/- 1.57 microns2; P = 0.30). On the other hand, both N-myc amplification and AgNOR protein expression were found to be significantly related to the clinical outcome of the disease (P < 0.001 and P = 0.0143, respectively; median follow-up time = 47 months; range 18-106 months). In a second set of experiments, the relationship between N-myc amplification and cell proliferation rate was assessed in seven established human neuroblastoma cell lines. N-myc amplification was found to be completely independent of the population doubling time (DT), which, on the contrary, was strictly related to the quantitative expression of AgNOR protein (r = -0.947; P < 0.001). Altogether, the present results indicate that N-myc amplification and cell proliferation rate are not interrelated in neuroblastoma, each representing an independent biological parameter of cancer cells associated with the clinical behaviour of the disease.
在神经母细胞瘤中，已发现N - myc基因扩增与肿瘤快速进展及预后不良显著相关。最近的研究表明，细胞增殖活性也能显著预测神经母细胞瘤患者的临床结局。为了明确N - myc基因扩增与细胞增殖率之间的相关性，在本研究中，首先对48例神经母细胞瘤肿瘤的这两个参数进行了评估。通过使用NB 19 - 21探针的Southern印迹分析在冷冻标本中评估N - myc基因扩增，在9例患者中检测到该扩增。通过测量银选择性染色的组织切片中的AgNOR蛋白面积来确定细胞增殖活性。有N - myc基因扩增的神经母细胞瘤的平均AgNOR蛋白面积值（3.63±1.62平方微米）与无N - myc基因扩增的神经母细胞瘤的平均AgNOR蛋白面积值（2.46±1.57平方微米；P = 0.30）无显著差异。另一方面，发现N - myc基因扩增和AgNOR蛋白表达均与疾病的临床结局显著相关（分别为P < 0.001和P = 0.0143；中位随访时间 = 47个月；范围18 - 106个月）。在第二组实验中，在7个人类神经母细胞瘤 established细胞系中评估了N - myc基因扩增与细胞增殖率之间的关系。发现N - myc基因扩增与群体倍增时间（DT）完全无关，相反，群体倍增时间与AgNOR蛋白的定量表达密切相关（r = - 0.947；P < 0.001）。总之，目前的结果表明，在神经母细胞瘤中N - myc基因扩增与细胞增殖率不相关，它们各自代表与疾病临床行为相关的癌细胞的独立生物学参数。
