Long-term survivors of glioblastoma multiforme: Clinical and molecular characteristics

Long-term survivors of glioblastoma multiforme: Clinical and molecular characteristics
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DOI:
10.1007/bf00165483
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发表时间:
1996-03-01
影响因子:
3.9
通讯作者:
Rosenfeld, MR
Rosenfeld, MR
中科院分区:
医学2区
文献类型:
--
作者:
Morita, M;Rosenblum, MK;Rosenfeld, MR

文献摘要

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多形性胶质母细胞瘤(GBM)患者的长期生存率很低。为了确定长期存活患者的肿瘤是否构成具有可识别分子遗传学特征的患者亚组,我们研究了GBM长期存活者的p53基因和表皮生长因子受体(EGF-R)表达。癌症和相关疾病纪念医院肿瘤登记处的一项综述记录了1954年至1987年间521例GBM患者接受治疗,12例患者存活7年或更长时间。从其他机构确定了另外6名长期幸存者。病理复查后,这18个肿瘤中的8个(44%)的诊断改变为其他组织学肿瘤类型。采用免疫组化分析,10例确诊的恶性胶质瘤中有4例p53过表达。聚合酶链反应/单链构象多态性(PCR/SSCP)分析和序列分析表明,这4个肿瘤没有p53突变的外显子5-8,该区域已报告的大多数突变在人类恶性肿瘤。对10例长期存活者的肿瘤进行EGF-R免疫组化分析。在4例(40%)中发现EGF-R过度表达,这与以前报道的GBM研究结果一致。这些结果表明,有一个子集的GBM定义的野生型p53的积累和EGF-R的过度表达并不妨碍长期生存。纪念医院肿瘤登记处确认的GBM患者的7年生存率至少为1%。
Long term survival is rare in patients with glioblastoma multiforme (GBM). To determine if the tumors of patients with long survivals constitute a subgroup of patients with identifiable moleculargenetic characteristics, we studied the p53 gene and Epidermal Growth Factor Receptor (EGF-R) expression in long-term survivors of GBM. A review of the Tumor Registry of Memorial Hospital for Cancer and Allied Diseases documented that 521 patients were treated for GBM between 1954 and 1987 and that 12 patients had seven-year or longer survivals. Six additional long-term survivors were identified from other institutions. After pathological re-examination, the diagnosis of 8 of these 18 (44%) tumors was changed to other histologic tumor types. Using immunohistochemical analysis, 4 of 10 confirmed malignant gliomas had over-expression of p53. Polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis and sequence analysis of these 4 tumors showed no p53 mutations in exons 5-8, the region where most mutations have been reported in human malignancies. Immunohistochemical analysis for EGF-R was performed on the tumors of the 10 long-term survivors. EGF-R over-expression was identified in 4 (40%), which is consistent with previous reported studies for GBM in general. These findings suggest that there is a subset of GBM defined by the accumulation of wild-type p53 and that the over-expression of EGF-R does not preclude long-term survival. The seven-year survival rate for confirmed GBM in patients from the Memorial Hospital Tumor Registry was at least 1%.