Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia
Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia
复制标题
DOI：
10.1093/jnen/63.5.441
复制
发表时间：
2004-05-01
影响因子：
3.2
通讯作者：
Burger, PC
中科院分区：
文献类型：
--
作者：
Eberhart, CG;Kratz, J;Burger, PC
一些分子和组织病理学预后标记物已经被提出用于髓母细胞瘤患者的治疗分层。C-myc癌基因扩增、c-myc信使核糖核酸水平升高或肿瘤间变与较差的临床结果相关。相反，TrkC mRNA的高表达通常预示着更长的生存时间。本研究的目的是评价c-myc、N-myc和TrkC在髓母细胞瘤中的表达对预后的预测价值，并与组织病理学分类进行比较。我们用原位杂交的方法来检测这些分子标记的表达。59例患者中有18例(31%)检测到c-myc基因的表达，单因素和多因素分析均显示c-myc基因表达与患者生存期缩短显著相关(p=0.04)。C-myc基因的表达与肿瘤间变显著相关。虽然低N-myc或高TrkC表达的患者存活率较高，但这些差异没有统计学意义。中度或重度间变性肿瘤患者组仅表现出生存期缩短的趋势(p=0.11)。然而，重度上皮化生本身具有显著的预后意义(p=0.002)。鉴于c-myc的预后重要性，我们研究了两种可能调节其表达的机制：WRIT信号和MXI-1突变。在c-myc高的髓母细胞瘤中，作为Wnt途径激活标志的β-catenin的核转位比在所有肿瘤中更常见，但差异无统计学意义。在所检测的22例病例中未检测到MXI-1突变。我们所描述的c-myc表达、肿瘤间变和较差的临床结果之间的关联为该癌基因在髓母细胞瘤病理生物学中的重要性提供了进一步的证据。
Several molecular and histopathological prognostic markers have been proposed for the therapeutic stratification of medulloblastoma patients. Amplification of the c-myc oncogene, elevated levels of c-myc mRNA, or tumor anaplasia have been associated with worse clinical outcomes. In contrast, high TrkC mRNA expression generally presages longer survival. The goal of this study was to evaluate the prognostic value of c-myc, N-myc and TrkC expression in medulloblastomas and compare them to histopathological classification. We used in situ hybridization to measure expression of these molecular markers. c-myc mRNA was detected in 18 of 59 (31%) cases, and was significantly associated with shorter patient survival times on both univariate and multivariate analyses (p = 0.04). The presence of c-myc mRNA was also significantly associated with tumor anaplasia. While survival rates were higher for patients with low N-myc or high TrkC expression, these differences were not statistically significant. The group of patients with either moderate or severely anaplastic tumors showed only a trend towards shorter survival (p = 0.11). However, severe anaplasia alone was significantly prognostic (p = 0.002). Given the prognostic import of c-myc, we investigated 2 potential mechanisms by which its expression might be regulated: Writ signaling and Mxi-1 mutation. Nuclear translocation of beta-catenin, a marker of Wnt pathway activation, was more common in medulloblastomas with high c-myc than in tumors overall, but the difference was not statistically significant. No Mxi-1 mutations were detected in the 22 cases examined. The association we describe between c-myc expression, tumor anaplasia, and worse clinical outcomes provides further evidence for the importance of this oncogene in medulloblastoma pathobiology.