Altungoz Oguz, Aygun Nevim, Tumer Sait, Ozer Erdener, Olgun Nur, Sakizli Meral
Department of Medical Biology and Genetics, Dokuz Eylul University, School of Medicine, 35340 Balcova, Izmir, Turkey.
Cancer Genet Cytogenet. 2007 Jan 15;172(2):113-9. doi: 10.1016/j.cancergencyto.2006.10.005.
Neuroblastoma (NB) is a childhood cancer derived from neural crest cells, with a highly variable clinical course and biologic behavior. NB cells harbor complex genetic changes. Also, MYCN amplification is a well-known molecular marker for aggressive progression, and deletion of the short arm of chromosome 1 is frequently observed in NB. The aim of this study was to investigate the correlation between genetic markers and prognostic morphological parameters to address the biology and underlying the clinical complexity of NB. Therefore, we performed fluorescence in situ hybridization analyses of chromosome band 1p36 and MYCN in a series of tumors from 43 cases classified according to the recommendation of International Neuroblastoma Pathology Committee (modification of Shimada classification). The correlations of MYCN amplification status and two distinct types of 1p36 alterations (deletion and imbalance) with Shimada classification and histologic prognostic factors were statistically analyzed. Amplification of MYCN and 1p36 deletion was present in 14 (32.6%) and 18 (41.9%) cases, respectively. Sixteen cases (37.2%) displayed a favorable histology, while 27 (62.8%) had an unfavorable histology. The 1p36 deletion was found to be an independent predictor of unfavorable histology by multivariate analysis (logistic regression test, P = 0.03), but the 1p36 imbalance did not show any significance. Both 1p36 deletion and MYCN amplification showed significant correlation with undifferentiated tumors (chi-square test, P = 0.002 and 0.03, respectively). Highly significant correlation was found between the higher mitotic karyorrhectic index (MKI) and MYCN amplification (chi-square test, P < 0.001), whereas neither 1p36 deletion nor 1p36 imbalance significantly correlated with a higher MKI (chi-square test, P > 0.05). We conclude that 1p36 deletion may be a reliable parameter in determining unfavorable histology and predicting prognosis in NB. Further studies with prognostic data are needed to highlight its clinical significance.
神经母细胞瘤（NB）是一种源自神经嵴细胞的儿童癌症，其临床病程和生物学行为高度可变。NB细胞存在复杂的基因变化。此外，MYCN扩增是侵袭性进展的一个众所周知的分子标志物，并且在NB中经常观察到1号染色体短臂的缺失。本研究的目的是调查基因标志物与预后形态学参数之间的相关性，以阐明NB的生物学特性及其临床复杂性的潜在原因。因此，我们根据国际神经母细胞瘤病理委员会的建议（岛田分类法的修订版），对43例肿瘤进行了1p36染色体带和MYCN的荧光原位杂交分析。对MYCN扩增状态以及两种不同类型的1p36改变（缺失和失衡）与岛田分类法和组织学预后因素之间的相关性进行了统计学分析。MYCN扩增和1p36缺失分别出现在14例（32.6%）和18例（41.9%）病例中。16例（37.2%）显示组织学良好，而27例（62.8%）组织学不良。多因素分析（逻辑回归检验，P = 0.03）发现1p36缺失是组织学不良的独立预测指标，但1p36失衡无显著意义。1p36缺失和MYCN扩增均与未分化肿瘤显示出显著相关性（卡方检验，P值分别为0.002和0.03）。有丝分裂核溶解指数（MKI）较高与MYCN扩增之间存在高度显著相关性（卡方检验，P < 0.001），而1p36缺失和1p36失衡与较高的MKI均无显著相关性（卡方检验，P > 0.05）。我们得出结论，1p36缺失可能是确定NB组织学不良和预测预后的一个可靠参数。需要进一步进行预后数据研究以突出其临床意义。
