脂肪肉瘤c-myc和p53基因蛋白的表达及意义

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（labelled streptavidin-biotin,LSAB)免疫组化法、聚合酶链反应－单链构象多态性分析（Single strand conformation polymorphism analysis of polymerase chain reaction products,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例显子第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用。脂肪肉瘤中p53基因第6、8外显子分别存在点突变。

Relationship between expression of c-myc and p53 in liposarcoma

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.