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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。
Objective To study the overexpression of epidermal growth factor receptor (EGFR) and the mutation of tumor suppressor gene p53 in astrocytoma and its relationship with tumor pathological type, malignancy and their relationship. Methods 37 cases of malignant astrocytic tumors and 6 cases of normal brain tissue were collected for immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry, PCR-SSCP, DNA sequencing method to detect the same specimen of p53 gene mutation and abnormal expression, analysis of their abnormal changes and internal relations. Results The mutation rate of p53 in diffuse astrocytoma, anaplastic astrocytoma, primary glioblastoma and secondary glioblastoma were 1 / 10,4 / 19 (21.1% ), 4/6 and 2/2 respectively, whereas EGFR overexpression was 5/10, 10/19 (52.6%), 5/6 and 2/2, respectively. With the increase of glioma grade, the incidence of p53 accumulation and EGFR overexpression in the same specimen increased. Conclusion The mutation of p53 gene is rare in low grade glioblastoma, and overexpression of EGFR is not uncommon. Mutations of p53 gene and overexpression of EGFR are common in both primary and secondary glioblastoma. It is suggested that the pathways of p53 and EGFR may not mutually exclude the malignant progression of glioma but synergistically promote them.