Mendez Gustavo, Ozpinar Alp, Raskin Jeffrey, Gultekin Sakir H, Ross Donald A
Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
Surg Neurol Int. 2014 Aug 2;5:121. doi: 10.4103/2152-7806.138034. eCollection 2014.
Diagnosis of glioblastoma multiforme (GBM) includes a heterogeneous group of tumors. We describe two cases with histopathologically and molecularly similar tumors, but very different outcomes. We attempt to illustrate the need for improved prognostic markers for GBM.
Two patients with similar molecular profiles were retrospectively identified. The following markers were assessed: O (6)-methylguanine DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) 1 and 2 status, epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) status, Ki-67, p53, and 1p/19q status. Each patient was assigned a Karnofsky performance score at presentation. Case 1 (62-year-old male) was a right temporal lobe glioblastoma with a molecular profile of amplified EGFR, normal PTEN, no IDH1/2 mutation, 28.7% MGMT promoter methylation, 5-20% Ki-67, 1p deletion, and 19q intact. The patient underwent resection followed by radiation therapy and 2 years of chemotherapy, and was asymptomatic and tumor free 5 years post diagnosis. Tumor eventually recurred and the patient expired 72 months after initial diagnosis. Case 2 (63-year-old male) was a right frontal white matter mass consistent with glioblastoma with a molecular profile of amplified EGFR, absent PTEN, no IDH1/2 mutation, 9.9% MGMT promoter methylation, 5-10% Ki-67, and 1p/19q status inconclusive. A radical subtotal resection was performed; however, 2 weeks later symptoms had returned. Subsequent imaging revealed a tumor larger than at diagnosis. The patient expired 3 months after initial diagnosis.
The need for formulating more robust means to classify GBM tumor subtypes is paramount. Standard histopathologic and molecular analyses are costly and did not provide either of these patients with a realistic appraisal of their prognosis. Individualized whole genome testing similar to that being reported for medulloblastoma and other tumors may be preferable to the array of tests as currently utilized.
多形性胶质母细胞瘤（GBM）的诊断包括一组异质性肿瘤。我们描述了两例组织病理学和分子特征相似但预后截然不同的病例。我们试图说明GBM需要改进的预后标志物。
回顾性确定了两名分子特征相似的患者。评估了以下标志物：O（6）-甲基鸟嘌呤DNA甲基转移酶（MGMT）甲基化、异柠檬酸脱氢酶（IDH）1和2状态、表皮生长因子受体（EGFR）扩增、磷酸酶和张力蛋白同源物（PTEN）状态、Ki-67、p53以及1p/19q状态。每位患者在就诊时都被赋予了卡诺夫斯基表现评分。病例1（62岁男性）为右颞叶胶质母细胞瘤，分子特征为EGFR扩增、PTEN正常、无IDH1/2突变、MGMT启动子甲基化28.7%、Ki-67为5-20%、1p缺失且19q完整。患者接受了手术切除，随后进行了放射治疗和2年化疗，诊断后5年无症状且无肿瘤。肿瘤最终复发，患者在初次诊断后72个月死亡。病例2（63岁男性）为右额叶白质肿块，符合胶质母细胞瘤，分子特征为EGFR扩增、PTEN缺失、无IDH1/2突变、MGMT启动子甲基化9.9%、Ki-67为5-10%，1p/19q状态不确定。进行了根治性次全切除；然而，2周后症状复发。随后的影像学检查显示肿瘤比诊断时更大。患者在初次诊断后3个月死亡。
制定更可靠的方法来分类GBM肿瘤亚型至关重要。标准的组织病理学和分子分析成本高昂，且未为这两名患者提供对其预后的实际评估。类似于目前报道的髓母细胞瘤和其他肿瘤的个体化全基因组检测可能比目前使用的一系列检测更可取。
