Nakagawara A, Sasazuki T, Akiyama H, Kawakami K, Kuwano A, Yokoyama T, Kume K
Department of Pediatric Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Cancer. 1990 May 1;65(9):1960-7. doi: 10.1002/1097-0142(19900501)65:9<1960::aid-cncr2820650914>3.0.co;2-4.
We studied the clinical significance of genomic amplification of N-myc in Stage IV-S neuroblastoma, with reference to spontaneous regression. Among 103 neuroblastomas in which N-myc was measured, ten were Stage IV-S (eight children were younger than and two were older than 1 year of age). The number of copies of N-myc was 1 to 3 in five patients, four to ten in one patient, and more than ten in four patients, and the survivors of each group were four, one, and one (recurrent), respectively. Of 41 patients younger than 1 year of age, N-myc amplification of more than three copies was found only in Stage IV-S neuroblastoma. Cure with a tendency to regress spontaneously was seen in five of eight patients younger than 1 year of age. However, two patients older than 1 year of age classified as Stage IV-S (one with N-myc amplification) died of progressive disease. In two patients (1 and 3 months of age) with a huge hepatic involvement and in whom the tumor had an amplified N-myc of more than ten copies, tumor regression occurred but there was a relapse to a progressive state later. The overexpression of N-myc mRNA occurred in nine of ten stage IV-S tumors and did not correlate with the prognosis. The vanillylmandelic acid (VMA) to homovanillic acid (HVA) ratio was low in tumors with an increased number of copies of N-myc. Serum lactate dehydrogenase (LDH) levels were increased in Stage IV-S patients with N-myc amplification but not in those with regressing tumors and without N-myc amplification. These data suggest that N-myc amplification may affect the final outcome in the patient classified as Stage IV-S, but tumor regression can occur early after birth and appears to be independent of N-myc amplification.
我们参照自然消退情况，研究了Ⅳ-S期神经母细胞瘤中N-myc基因扩增的临床意义。在检测了N-myc的103例神经母细胞瘤中，有10例为Ⅳ-S期（8例患儿年龄小于1岁，2例患儿年龄大于1岁）。5例患者的N-myc拷贝数为1至3个，1例患者为4至10个，4例患者大于10个，每组的存活者分别为4例、1例和1例（复发）。在41例年龄小于1岁的患者中，仅在Ⅳ-S期神经母细胞瘤中发现N-myc扩增超过3个拷贝。8例年龄小于1岁的患者中有5例出现了有自然消退倾向的治愈情况。然而，2例年龄大于1岁且被归类为Ⅳ-S期的患者（1例有N-myc扩增）死于疾病进展。在2例肝脏有巨大受累且肿瘤N-myc扩增超过10个拷贝的患者（年龄分别为1个月和3个月）中，肿瘤出现了消退，但后来又复发至进展状态。10例Ⅳ-S期肿瘤中有9例出现N-myc mRNA过表达，且与预后无关。N-myc拷贝数增加的肿瘤中香草扁桃酸（VMA）与高香草酸（HVA）的比值较低。Ⅳ-S期N-myc扩增患者的血清乳酸脱氢酶（LDH）水平升高，但肿瘤消退且无N-myc扩增的患者中LDH水平未升高。这些数据表明，N-myc扩增可能会影响Ⅳ-S期患者的最终结局，但肿瘤消退可在出生后早期出现，且似乎与N-myc扩增无关。
