Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenação Geral Técnico-Científica, Instituto Nacional de Câncer, Praça da Cruz Vermelha, 23, 6o andar, Ala B, Centro, 20230-130 Rio de Janeiro, RJ, Brazil.
Pathol Oncol Res. 2011 Dec;17(4):899-908. doi: 10.1007/s12253-011-9401-z. Epub 2011 Jun 17.
Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children. Because of the significant rate of mortality and treatment-related morbidity, the identification of prognostic factors could lead to a more accurate selection of patients who can benefit from a less aggressive therapy and improve risk stratification. Survivin is an inhibitor of apoptosis protein (IAP), the expression of which has been associated with worse prognosis in MDB. However, both of its subcellular localizations may contribute to tumor progression, and ultimately, survivin subcellular localization prognostic value depends on tumor type biological features. The goal of this study was to analyze these survivin features in the pediatric MDB tumor samples and its impact on clinical outcome. Survivin expression and subcellular localization were accessed by immunohistochemistry in a series of 41 tumor samples. Kaplan-Meier survival curves were compared using the log-rank test. Survivin expression ranged from completely absent to fully present in a notably higher pattern of nuclear localization than cytoplasmic (19 of 41 versus 4 of 41, respectively). However, survivin expression and subcellular localization were not associated with five-year overall survival or metastasis status at diagnosis, which was the only statistically significant prognostic factor in our series (p = 0.008). Taken together, our results suggest that survivin expression should be further studied in large, multicenter series to determine its accurate impact on prognosis and pathobiology of pediatric MDB.
髓母细胞瘤（MDB）是儿童中最常见的恶性小脑肿瘤。由于死亡率和治疗相关发病率高，因此识别预后因素可以更准确地选择可以从较少侵袭性治疗中受益并改善风险分层的患者。Survivin 是凋亡抑制蛋白（IAP），其表达与 MDB 的预后不良相关。然而，其亚细胞定位都可能促进肿瘤进展，最终，Survivin 亚细胞定位的预后价值取决于肿瘤类型的生物学特征。本研究的目的是分析小儿 MDB 肿瘤样本中的这些 Survivin 特征及其对临床结果的影响。通过免疫组织化学在一系列 41 个肿瘤样本中检测 Survivin 的表达和亚细胞定位。使用对数秩检验比较 Kaplan-Meier 生存曲线。Survivin 的表达范围从完全缺失到完全存在，核定位明显高于细胞质（分别为 41 例中的 19 例和 41 例中的 4 例）。然而，Survivin 的表达和亚细胞定位与五年总生存率或诊断时的转移状态无关，这是我们研究系列中唯一具有统计学意义的预后因素（p=0.008）。综上所述，我们的研究结果表明，应该在大型多中心系列中进一步研究 Survivin 的表达，以确定其对小儿 MDB 的预后和病理生物学的准确影响。
