【摘要】 目的研究星形细胞肿瘤中癌基因表皮生长因子受体(EGFR)过表达与抑癌基因p53突变、表达与肿瘤病理类型、恶性程度及两者的相互关系。方法对37例不同恶性程度的星形细胞肿瘤及6例正常脑组织,采用免疫组织化学、逆转录聚合酶链反应(RT-PCR)方法检测EGFR的表达;采用免疫组织化学、PCR-SSCP及DNA测序方法检测同一标本的p53基因突变和异常表达,分析它们的异常改变和内在联系。结果p53突变率在弥漫性星形细胞瘤、间变性星形细胞瘤、原发性胶质母细胞瘤、继发性胶质母细胞瘤分别为1/10,4/19(21·1%),4/6和2/2,而EGFR过表达分别为5/10,10/19(52·6%),5/6和2/2。随着胶质瘤级别增高,p53积聚与EGFR过表达在同一标本中发生率升高。结论在低度恶性胶质瘤中p53基因突变少见,EGFR过表达不少见;在原发性和继发性胶质母细胞瘤中p53基因突变及EGFR过表达均常见。提示p53与EGFR分子通路可能对胶质瘤的恶性进展不是相互排斥而是协同产生促进作用。更多还原

【Abstract】 Objective To study further the most important and frequent genetic alterations of p53 and epidermal growth factor receptor (EGFR) in astrocytic gliomas. Methods (1)EGFR expression was examined in samples collected from 37 astrocytic gliomas and 6 normal brain tissue using reverse transcriptase polymerase chain reaction and immunohistochemical staining. (2) p53 gene mutation and accumulation were detected simultaneously in the same specimens using PCR-SSCP, DNA sequencing and immunohistochemical staining. Results The frequency of p53 mutation in diffuse astrocytomas, anaplastic astrocytomas, primary glioblastomas and secondary glioblastomas was 1/10, 4/19(21.1%), 4/6 and 2/2, respectively and the frequency of EGFR overexpression was 5/10, 10/19(52.6%), 5/6 and 2/2, respectively. Both p53 accumulation and EGFR overexpression increased accompanied by a successive increase of degree of the glioma malignancy. Conclusions EGFR overexpression is not infrequently seen, however, p53 mutation is rarely seen in the low grade gliomas. Both p53 gene mutation and EGFR overexpression are often associated with primary and secondary glioblastoma. Consequently,EGFR overexpression and p53 gene mutation are not mutually exclusive in astrocytic gliomagenesis but synergistically to promote the glioma progression.更多还原