Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing
Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing
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DOI：
10.1007/s11060-014-1451-0
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发表时间：
2014-06-01
影响因子：
3.9
通讯作者：
McCutcheon, Ian E.
中科院分区：
文献类型：
--
作者：
Kim, Betty Y. S.;Jiang, Wen;McCutcheon, Ian E.
恶性星形细胞瘤的准确分级具有重要的预后和治疗意义。由于区域肿瘤异质性，传统的组织病理学分级可能具有挑战性，特别是在少量组织可用于病理检查的情况下。在这里，我们假设一个关键的肿瘤切除体积是需要正确的分级星形细胞瘤的组织病理学。对于组织采样不足，IDH 1分子检测可以作为补充标志物，以提高诊断准确性。使用术前和术后MRI图像获得体积分析。收集了403例接受开颅手术的恶性星形细胞瘤患者的组织学标本。IDH 1状态通过免疫组织化学和测序进行评估。在MRI上切除的肿瘤总体积> 20立方厘米（cc）的患者与< 20 cc的患者相比具有更高的GBM诊断率[比值比（OR）2.57，95%置信区间（CI）1.6-4.06，P < 0.0001]。IDH 1状态的发生率与切除肿瘤体积无关（OR 0.81，95%CI 0.48-1.36，P < 0.43）。单个手术标本> 10 cc的GBM诊断率是小体积标本的2倍（OR 2.48，95%CI 1.88-3.28，P < 0.0001）。MRI上肿瘤切除> 20 cc的AA患者的总生存率明显优于肿瘤切除< 20 cc的患者（P < 0.05）。在GBM（P < 0.4）、IDH 1野生型（P < 0.1）和IDH 1突变型（P < 0.88）患者中未观察到体积依赖性差异。根据MRI分析，当总切除量< 20 cc时，以及手术标本< 10 cc时，应考虑IDH 1状态，以补充恶性星形细胞瘤的组织病理学诊断。在这些标本中，当分析仅限于组织病理学时，可能发生GBM诊断不足。
The accurate grading of malignant astrocytomas has significant prognostic and therapeutic implications. Traditional histopathological grading can be challenging due to regional tumor heterogeneity, especially in scenarios where small amounts of tissue are available for pathologic review. Here, we hypothesized that a critical tumor resection volume is needed for correct grading of astrocytomas by histopathology. For insufficient tissue sampling, IDH1 molecular testing can act as a complementary marker to improve diagnostic accuracy. Volumetric analyses were obtained using preoperative and postoperative MRI images. Histological specimens were gathered from 403 patients with malignant astrocytoma who underwent craniotomy. IDH1 status was assessed by immunohistochemistry and sequencing. Patients with > 20 cubic centimeters (cc) of the total tumor volume resected on MRI have higher rate of GBM diagnosis compared to < 20 cc [odds ratio (OR) 2.57, 95 % confidence interval (CI) 1.6-4.06, P < 0.0001]. The rate of IDH1 status remained constant regardless of the tumor volume resected (OR 0.81, 95 % CI 0.48-1.36, P < 0.43). The rate of GBM diagnosis is twofold greater for individual surgical specimen > 10 cc than those of lower volume (OR 2.48, 95 % CI 1.88-3.28, P < 0.0001). Overall survival for AA patients with > 20 cc tumor resection on MRI is significantly better than those with < 20 cc tumor resected (P < 0.05). No volume-dependent differences were observed in patients with GBM (P < 0.4), IDH1 wild type (P < 0.1) or IDH1 mutation (P < 0.88). IDH1 status should be considered when total resection volume is < 20 cc based on MRI analysis and for surgical specimen < 10 cc to complement histopathologic diagnosis of malignant astrocytomas. In these specimens, under-diagnosis of GBM may occur when analysis is restricted to histopathology alone.