Molecular biologic prognostic factors in soft tissue sarcomas

软组织肉瘤的分子生物学预后因素

• 批准号: 12670167
• 负责人: ODA Yoshinao
• 金额: $ 2.11万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670167/
• 关键词: Soft tissue sarcoma; p53; MDM2; H-ras; Prognosis; Synovial sarcoma; beta-catenin; Malignant peripheral nerve sheath tumor; 悪性軟部腫瘍; 平滑筋肉腫; PTEN; MMAC1; 胞巣状軟部肉腫; DNAミスマッチ修復遺伝子; hMLH1; hMSH2; 悪性線維性組織球種; 多形型平滑筋肉腫; 皮膚異型繊維性黄色腫; 炎症性筋線維芽細胞性腫瘍 /

We have carried out extensive investigations into the molecular biologic characteristics of several kinds of soft-tissue sarcomas and the following results have been obtained.1. Dedifferentiated liposarcoma or chondrosarcoma: The frequency of p53 gene alterations and H-ras gene alteration in dedifferentiated component was higher than those in well differentiated component within the same tumor.2. Synovial sarcoma: The detection of SYT-SSX fusion transcripts is a useful diagnostic tool in this tumor, however, its subtype has no correlation with patient's prognosis. An increased rate of apoptosis, a low p27/kip1-labeling index, reduced expression of E-cadherin and alpha-catenin, aberrant expression of beta-catenin, beta-catenin gene mutation, and co-expression of hepatocyte growth factor (HGF) and c-MET are all adverse prognostic factors. E-cadherin gene alteration has no correlation with prognosis, however, it is one of the causes of epithelial-mesenchymal transition in this tumor. Molecular abnormalities of p53, MDM2 and ras gene have no correlation with prognosis.3. Malignant rhabdoid tumor (MRT):p53 gene alterations occur frequently. All examined cases showed hSNF5/INI1 gene alterations.4. Malignant peripheral nerve sheath tumor (MPNST): The expression of p53 protein, TGF- beta 1, TGF-beta receptor type II, HGF and c-MET is higher in the areas of MPNST than in the neurofibromatous areas within the same tumor in patients with von Recklinghausen's disease. High MIB-1 labeling index and the presence of rhabdomyoblasts (Malignant Triton tumor) were adverse prognostic factors in MPNST. The alteration of p53 did not affect the patients survival.5. Sporadic desmoid tumor: Beta-catenin accumulation has a significant relationship with cyclin D1 overexpression. In a beta-catenin mutated group, cyclin D1 mRNA expression was found to be significantly higher than that in a beta-catenin wild-type group.

我们对几种软组织肉瘤的分子生物学特征进行了广泛的研究，取得了以下结果.去分化脂肪肉瘤或软骨肉瘤：同一肿瘤中去分化组p53基因和H-ras基因的改变频率高于高分化组.滑膜肉瘤：SYT-SSX融合基因的检测是一个有用的诊断工具，但其亚型与患者的预后无关。细胞凋亡率增加、p27/kip 1标记指数降低、E-钙粘蛋白和α-连环蛋白表达减少、β-连环蛋白表达异常、β-连环蛋白基因突变、肝细胞生长因子（HGF）和c-MET共表达均为不良预后因素。E-cadherin基因的改变与预后无关，但可能是导致上皮间质转化的原因之一。p53、MDM 2和ras基因的分子异常与膀胱癌的发生无关.恶性横纹肌样瘤（MRT）：p53基因改变频繁发生。所有受检病例均存在hSNF 5/INI 1基因变异.恶性周围神经鞘瘤（MPNST）：在von Recklinghausen病患者的MPNST区域中，p53蛋白、TGF-β 1、TGF-β II型受体、HGF和c-MET的表达高于同一肿瘤内的神经纤维瘤区域。高MIB-1标记指数和横纹肌母细胞（恶性Triton瘤）的存在是MPNST的不良预后因素。p53的改变不影响患者的生存率.散发性硬纤维瘤：β-连环蛋白积聚与细胞周期蛋白D1过表达有显著关系。在β-连环蛋白突变组中，发现细胞周期蛋白D1 mRNA表达显著高于β-连环蛋白野生型组。

项目成果

Sakamoto A, Oda Y, Adachi T, Oshiro Y, Tamiya S, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M: "H-ras oncogene mutation in dedifferentiated chondrosarcoma : Polymerase chain reaction-restriction fragment length polymorphism analysis"Mod Pathol.. 14. 343-3

Sakamoto A、Oda Y、Adachi T、Oshiro Y、Tamiya S、Tanaka K、Matsuda S、Iwamoto Y、Tsuneyoshi M：“去分化软骨肉瘤中的 H-ras 癌基因突变：聚合酶链反应-限制性片段长度多态性分析”Mod Pathol。

Oda Y, Sakamoto A, Saito T, Kawauchi S, Iwamoto Y, Tsuneyoshi M: "Molecular abnormalities of p53, MDM2 and H-ras in synovial sarcoma"Mod Pathol. 13. 994-1004 (2000)

Oda Y、Sakamoto A、Saito T、Kawauchi S、Iwamoto Y、Tsuneyoshi M：“滑膜肉瘤中 p53、MDM2 和 H-ras 的分子异常”Mod Pathol。

Watanabe T et al.: "Malignant peripheral nerve sheath tumors : high ki67 labelling index is the significant prognostic indicator"Histopathology. 39. 187-197 (2001)

Watanabe T 等人：“恶性周围神经鞘瘤：高 ki67 标记指数是重要的预后指标”组织病理学。

Saito T, Oda Y et al.: "Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in soradic desmoid tumors : Real-time semiquantative assay by TaqMan PCR"Laboratory Investigation. 82. 97-103 (2002)

Saito T、Oda Y 等人：“Soradic 硬纤维瘤中较高的 β-连环蛋白 mRNA 表达与突变的 β-连环蛋白之间的可能关联：通过 TaqMan PCR 进行的实时半定量测定”实验室研究。

Kinoshita K, Shiratsuchi H, Tamiya S, Oshiro Y, Oda Y, Suita S, Tsuneyoshi M: "Establishment and characterization of malignant rhabdoid tumor of the kidney : Immunohistochemical and cytogenetical analysis"Oncology Reports. 8. 43-48 (2001)

Kinoshita K、Shiratsuchi H、Tamiya S、Oshiro Y、Oda Y、Suita S、Tsuneyoshi M：“肾脏恶性横纹肌瘤的建立和特征：免疫组织化学和细胞遗传学分析”肿瘤学报告。