恶性间皮瘤p53基因点突变和蛋白表达

p53基因是在人类多数肿瘤中发生高频突变的肿瘤相关性最强的抑癌基因，其突变特征为80%的点突变均集中在进化的高保区内，即对应的第5-8外显子部位. 恶性间皮瘤是一种与接触石棉有明确关系的间叶源性肿瘤. 为深入阐明p53基因在人恶性间皮瘤发生发展中的作用，应用聚合酶链反应-单链构象多态性(PCR-SSCP)和免疫组化技术研究了34例恶性间皮瘤p53 基因的点突变情况. 结果表明： 56%(19/34)的病例存在p53基因的点突变，突变率在不同的组织学类型之间有一定的差异；在所发现的22次突变中有16次均发生在第7外显子，表明第7外显子是本组恶性间皮瘤的突变热点所在；免疫组化染色：23%（8/34）的病例P53蛋白免疫组化染色为阳性，阳性率低于基因突变率. 以上资料提示p53基因突变可能在恶性间皮瘤的癌变机制中起着重要作用.

Gene p53 point mutation and protein expression in human malignant mesothelioma

A putative tumor suppressor gene, p53, has been shown to be altered in variety of human tumor types. It may even be the commonest mutant gene in human cancers. About 80% of p53 point mutation events seem to cluster predominantly around several highly conserved amino acid domains which include exons 5-8. Malignant mesothelioma is a mesenchymal neoplasm which is highly associated with exposure to asbestos fibers. In this study, 34 individuals with malignant mesothelioma hve been examined for p53 mutations by silver stain polymerase chain reaction single strand conformation polymorphism (PCR SSCP) techniques. Results showed p53 point mutations in cases from 19 individuals, the total mutation rate was 56% and different among three histological types of neoplasm. Among 22 detected mutations,16 mutations were found in exon 7, the mutation frequency of exon 7 was much higher than that of other exons. It suggested that in these malignant mesothelioma cases p53 gene mutation hot spot be in exon 7. The mutation bands of exon 7 indicated that its mutation type was heterozygosity. P53 protein expression was detected by immunohistochemical stain and results showed that the total positive staining rate was 23% (8/34), the protein positive rate was much lower than the gene mutation rate. These data reveal that p53 gene mutation may constitute a critical step in the development of human mesothelioma.