Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas.
Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas.
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DOI：
10.1097/pas.0b013e318294e817
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Quezado MM
中科院分区：
文献类型：
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作者：
Ballester LY;Wang Z;Shandilya S;Miettinen M;Burger PC;Eberhart CG;Rodriguez FJ;Raabe E;Nazarian J;Warren K;Quezado MM
中枢神经系统肿瘤是儿童中第二常见的恶性肿瘤。特别是，弥漫性内源性脑桥胶质瘤 (DIPG) 是一种预后不良的侵袭性肿瘤，占儿童脑肿瘤的 10-25%。大多数 DIPG 是星形胶质细胞、浸润性的并且局限于脑桥。研究表明，中位生存时间不到一年，90% 的儿童在 2 年内死亡。我们使用 24 个死后 DIPG 样本构建了多组织阵列，并分析了几种蛋白质（p53、EGFR、GFAP、MIB1、BMI1、B-catenin、p16、Nanog、Nestin、OCT4、OLIG2、Sox2）的形态和表达，目的是确定潜在的治疗靶点并提高我们对这些肿瘤生物学的了解。大多数 DIPG 为高级别胶质瘤（22 例），其中 18 例具有胶质母细胞瘤特征（WHO IV 级），4 例具有与间变性星形细胞瘤一致的高级别特征（WHO III 级）。 1例为低级别（WHO II级），1例表现出II级和III级胶质瘤之间的中间特征（有丝分裂率低，但细胞结构和细胞异型性增加），难以精确分级。大多数肿瘤呈GFAP（24/24）、MIB1（23/24）、OLIG2（22/24）、p16（20/24）、p53（20/24）阳性， Sox2 (19/24)、EGFR (16/24) 和 BMI1 (9/24)。我们的结果表明 EGFR 和 p53 的失调可能在 DIPG 的发生中发挥重要作用。大多数 DIPG 表达干细胞标记物，例如 SOX2 和 OLIG2，这与肿瘤干细胞在这些肿瘤的起源和维持中的作用一致。针对这些蛋白质的靶向治疗可能有益于治疗。
Tumors of the CNS are the second most common malignancy in children. In particular, diffuse intrinsic pontine gliomas (DIPGs) are aggressive tumors with poor prognosis and account for 10–25% of pediatric brain tumors. The majority of DIPGs are astrocytic, infiltrative and localized to the pons. Studies have shown median survival times of less than a year with 90% of children dying within 2 years. We built multi-tissue arrays with 24 post-mortem DIPG samples and analyzed the morphology and expression of several proteins (p53, EGFR, GFAP, MIB1, BMI1, B-catenin, p16, Nanog, Nestin, OCT4, OLIG2, Sox2) with the goal of identifying potential treatment targets and improving our understanding of the biology of these tumors. The majority of DIPGs were high-grade gliomas (22) with 18 cases having features of glioblastoma (WHO grade IV), and 4 cases with high-grade features consistent with anaplastic astrocytoma (WHO grade-III). One case was low grade (WHO grade II) and one case showed intermediate features between a grade II and grade III glioma (low mitotic rate, but increased cellularity and cell atypia), being difficult to grade precisely.. The majority of the tumors were positive for GFAP (24/24), MIB1 (23/24), OLIG2 (22/24), p16 (20/24), p53 (20/24), Sox2 (19/24), EGFR (16/24) and BMI1 (9/24). Our results suggest that dysregulation of EGFR and p53 may play an important role in the development of DIPGs. The majority of DIPGs express stem cell makers such as SOX2 and OLIG2, consistent with a role for tumor stem cells in the origin and maintenance of these tumors. Targeted therapies against these proteins could be beneficial in treatment.