脂肪肉瘤c-myc和p53基因蛋白的表达及意义

Relationship between Expression of c-myc and p53 in Liposarcoma

背景与目的:原癌基因c-myc和抑癌基因p53与脂肪肉瘤的关系的研究较少,脂肪肉瘤中是否存在p53基因突变文献报道不一,本文拟探讨脂肪肉瘤中c-myc、p53基因蛋白表达的水平及意义,以期为本组肿瘤发生发展及病理诊断、鉴别诊断提供一定的分子生物学资料。方法:采用链菌素抗生物素-生物素(labelledstreptavidin-biotin,LSAB)免疫组化法、聚合酶链反应-单链构象多态性分析(Singlestrandconformationpolymorphismanalysisofpolymerasechainreactionproducts,PCR-SSCP)及DNA序列分析方法。结果:c-myc和p53蛋白在脂肪肉瘤表达阳性率分别为38.09%(16/42)和48.08%(25/52)。不同类型脂肪肉瘤,分化良好者阳性率均明显低于分化较差者。脂肪肉瘤中c-myc和p53蛋白表达呈正相关。c-myc和p53蛋白表达在原发者和复发者之间的差异均无统计学意义。p53第6、7、8外显子PCR-SSCP分析,2例多形性脂肪肉瘤出现异常泳动带。DNA序列分析证实1例第8外显子第268位编码区出现错义突变(AAC→ATC),另1例第6外显子第221位编码区出现可疑杂合性同义突变(GAG→GAA)。结论:c-myc和p53蛋白与脂肪肉瘤的形成及分化和恶性程度有关,它们可作为判断脂肪肉瘤分化程度及恶性程度参考指标之一,但与肿瘤复发无关。在脂肪肉瘤发生发展中两者可能起协同作?

Background & Objective: The relationship between liposarcoma and gene c myc and p53 is not clear. There are also different reports on p53 mutation in liposarcoma. This study was designed to investigate the relationship between the expression of c myc and p53 genes and liopsarcomas. We hope to better understand the role of the c myc and p53 genes in molecular biology.Methods: Immunohistochemical labelled streptavidin biotin (LSAB) method, single strand conformation polymorphism analysis of polymerase chain reaction products (PCR SSCP), and DNA sequencing were used. Results: 38.09%(16/42) liposarcoma samples detected were immunohistochemically c myc protein positive. p53 protein was detected in 52 liposarcomas with the positive staining rate of 48.08%(25/52). In different subtypes of liposarcomas, the positive staining rates of c myc and p53 gene proteins were much lower in well differentiated liposarcomas than in the poorly differentiated liposarcomas. There was a positive correlation between c myc and p53 expression in liposarcoma. There was no statistical significance for the different positive staining rate of c myc and p53 protein in the primary and the recurrent liposarcoma. Abnomality in the single stranded DNA pattern was determined by PCR SSCP analysis in 2 samples (pleomophic liposarcomas) . Missense mutation in exon 8 of codon 268 of p53 gene (AAC→ATC)were detected by DNA sequencing. Another heterozygotic cosense mutation may exist at exon 6 of codon 221 of p53 gene (GAG→GAA). Conclusions: The c myc and p53 protein are associated with the development, differentiation, and malignancy of liposarcoma, but not with the recurrence of liposarcoma. Detecting the level of c myc and p53 protein expression may be valuable in evaluating the level of differentiation and malignancy of liposarcoma. c myc and p53 play synergic roles in the cooperation of development of liposarcoma. There appear the point mutation on exon 8, 6 of p53 gene.