Correlation of γ-catenin expression with good prognosis in medulloblastomas
Correlation of γ-catenin expression with good prognosis in medulloblastomas
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DOI：
10.3171/jns.2005.102.2.0197
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发表时间：
2005-03-01
影响因子：
4.1
通讯作者：
Fujisawa, H
中科院分区：
文献类型：
--
作者：
Misaki, K;Marukawa, K;Fujisawa, H
Object.髓母细胞瘤是一种发生于儿童小脑的恶性肿瘤，由于其频繁的脑脊液扩散而难以治愈。已知c-myc基因扩增（4%）和信使（mRNA）过表达（50%）是不良预后指标。由于mRNA的过度表达不能单独用基因扩增来解释，因此假设了基因扩增以外的机制。检测原发性肿瘤中Wnt信号通路的分子。对24例原发性髓母细胞瘤进行β-和γ-连环蛋白、c-myc、N-myc和细胞周期蛋白D1的免疫组织化学和细胞遗传学检查，并评价其临床意义。19例（79%）和9例（37%）分别检测到β-和γ-连环蛋白的胞质/膜染色，6例（25%）和21例（83%）分别检测到细胞周期蛋白D1和c-myc的核表达。免疫印迹和免疫组化结果显示γ-连环蛋白的表达水平相似。应用差异聚合酶链反应（PCR）技术，在两例大细胞间变性髓母细胞瘤中分别扩增出c-myc和N-myc基因。Kaplan-Meier分析显示诊断时无播散（Chang分级MO），γ-连环蛋白表达与良好预后相关（分别为p = 0.0002和0.003）。γ-连环蛋白的表达在MO组中也是显著的（p = 0.022）。细胞周期蛋白D1的表达显示了不良结局的趋势（p = 0.057），所有发现细胞周期蛋白D1表达的患者均死于疾病。γ-连环蛋白的表达具有很大的预后价值，其免疫组化可能有助于进一步分层的治疗。细胞周期蛋白D1的表达可能是一个不利的预后指标。
Object. Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined.Methods. Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade MO) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the MO group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease.Conclusions. Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D1 expression may have the potential to be an adverse prognostic indicator.