Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma
Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma
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DOI：
10.1007/s00401-014-1326-7
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发表时间：
2014-10-01
影响因子：
12.7
通讯作者：
von Deimling, Andreas
中科院分区：
文献类型：
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作者：
Sahm, Felix;Reuss, David;von Deimling, Andreas
星形细胞瘤和少突胶质细胞瘤是组织学和遗传学上明确定义的实体。大多数星形细胞瘤同时存在 TP53 和 ATRX 突变，而大多数少突胶质细胞瘤携带 1p/19q 共缺失。两个实体都具有高频率的 IDH 突变。相比之下，少突星形细胞瘤（OA）的定义似乎不太明确，因此，这些肿瘤是否确实构成一个实体，或者它们是否代表包含星形细胞瘤和少突胶质细胞瘤的混合体，一直存在争论。我们采用组织学、免疫组织化学和原位杂交技术研究了在不同机构诊断的 43 例 OA，寻找分子遗传标记 IDH1R132H、TP53、ATRX 和 1p/19q 缺失的替代物。在除一种 OA 之外的所有 OA 中，核 p53 积累和 ATRX 丢失的组合与 1p/19q 共缺失是相互排斥的。在 31/43 OA 中，仅观察到少突胶质细胞瘤的典型改变，而在 11/43 OA 中，仅检测到星形细胞瘤典型的突变指标。单个病例表现出独特的模式：p53 的核表达、ATRX 缺失、IDH1 突变和部分 1p/19q 缺失。然而，这是唯一一位在手术前接受放射治疗的患者，可能有助于获得这种不常见的组合。在具有少突胶质细胞瘤典型改变的OA中，对应于星形细胞部分的部分被确定为反应性的，而在具有星形细胞瘤典型改变的OA中，对应于少突胶质细胞分化的部分是肿瘤性的。这些数据提供了强有力的证据来证明独立OA实体的存在。
Astrocytoma and oligodendroglioma are histologically and genetically well-defined entities. The majority of astrocytomas harbor concurrent TP53 and ATRX mutations, while most oligodendrogliomas carry the 1p/19q co-deletion. Both entities share high frequencies of IDH mutations. In contrast, oligoastrocytomas (OA) appear less clearly defined and, therefore, there is an ongoing debate whether these tumors indeed constitute an entity or whether they represent a mixed bag containing both astrocytomas and oligodendrogliomas. We investigated 43 OA diagnosed in different institutions employing histology, immunohistochemistry and in situ hybridization addressing surrogates for the molecular genetic markers IDH1R132H, TP53, ATRX and 1p/19q loss. In all but one OA the combination of nuclear p53 accumulation and ATRX loss was mutually exclusive with 1p/19q co-deletion. In 31/43 OA, only alterations typical for oligodendroglioma were observed, while in 11/43 OA, only indicators for mutations typical for astrocytomas were detected. A single case exhibited a distinct pattern, nuclear expression of p53, ATRX loss, IDH1 mutation and partial 1p/19q loss. However, this was the only patient undergoing radiotherapy prior to surgery, possibly contributing to the acquisition of this uncommon combination. In OA with oligodendroglioma typical alterations, the portions corresponding to astrocytic part were determined as reactive, while in OA with astrocytoma typical alterations the portions corresponding to oligodendroglial differentiation were neoplastic. These data provide strong evidence against the existence of an independent OA entity.