Molecular and pathologic analysis of growth factors on the proliferating activities and metastases in bone and soft tissue sarcomas

结合临床病理分析，应用分子生物学技术评价骨和软组织肿瘤的生物学特性。恶性转化：1)神经纤维瘤向恶性周围神经鞘膜瘤转化；P53蛋白异常表达；2)隆起皮肤纤维肉瘤向纤维肉瘤转化；染色体异常。以高度恶性为特征的去分化软骨肉瘤和去分化脂肪肉瘤：H-ras突变。肉瘤的生物学行为1)平滑肌肉瘤：4例死亡病例中有P53突变，均为浅表型。实时荧光定量RT-PCR结果显示，P53基因表达水平升高与P53蛋白过度表达相关。2)滑膜肉瘤：预后不良因素：(1)AJC分期高，(2)肿瘤体积大，(3)HGF/c-MET共表达，(4)p53、MDM2、H-ras、β-连环素突变。3)恶性横纹肌样瘤(I)细胞角蛋白8和18的免疫表达，(Ii)三维成像显示细胞角蛋白和波形蛋白在横纹肌样细胞中的亚细胞分布，(Iii)波形蛋白和细胞角蛋白的基因组异常，(Iv)预后不良因素：β-catenin、p53、hSNF5/INI1的异常表达；4)骨肉瘤：nm23、c-met在转移和肿瘤进展中的显著意义。

We assessed the biological character of bone and soft tissue tumors by molecular biology technique in addition to clinico-pathologic analysis.1. Malignant transformation : 1) Neurofibroma to malignant peripheral nerve sheath tumor ; abnormal expression of p53 protein, 2) Dermatofibrosarcoma protuberans to fibrosarcoma ; chromosomal abnormality.2. Dedifferentiated chondrosarcoma and dedifferentiated liposarcoma characterized by high grade malignancy : H-ras mutation3. Biological behavior in sarcomas1) Leiomyosarcoma : p53 mutation in 4 dead cases among favorable superficial type. Using Real-Time Semi-quantitative RT-PCR, an increasing level of p53 mRNA associated with an overexpression of p53 protein. 2) Synovial sarcoma : Unfavorable prognostic factors (i) high AJC stage, (ii) large tumor size, (iii) co-expression of HGF/c-MET, (iv) mutation of p53, MDM2, H-ras, beta-catenin. 3) Malignant rhabdoid tumor (i) Immunoexpression of cytokeratin 8 and 18, (ii) Subcellular distribution of cytokeratin and vimentin in rhabdoid cell by three-dimensional imaging, (iii) Genomic abnormality of vimentin and cytokeratin, (iv) Unfavorable prognostic factors : abnormal expression of beta-catenin, p53, hSNF5/INI1 4)Osteosarcoma : Significant nm23, c-MET in metastasis and tumor progression.