骨巨细胞瘤TIMP-3启动子甲基化的研究

目的 检测骨巨细胞瘤(GCT)中TIMP—3启动子甲基化及其蛋白表达，探讨该肿瘤组织TIMP—3蛋白表达缺失的原因和TIMP-3启动子甲基化与GCT分级和复发的关系。方法 用免疫组织化学SP法和蛋白免疫印迹检测TIMP—3在GCT组织中的表达，用甲基化特异的PCR(MSP)法检测TIMP—3基因启动子的甲基化状态。结果 TIMP—3主要在单核基质细胞和多核巨细胞的胞质表达，后者的表达具有明显的极向性。17例GCT中有5例(29．4％)TIMP—3蛋白丢失，其中4例的TIMP—3启动子发生异常甲基化，且均为组织学分级为Ⅱ级的病例。结论 GCT的局部骨质破坏，可能与TIMP—3丢失有关；而TIMP—3启动子的异常甲基化，是TIMP—3基因失活和蛋白丢失的重要机制。

Promoter methylation of TIMP-3 gene in giant cell tumors of bone

Purpose To detect aberrant promoter methylation of the gene by tissue inhibitor of metalloproteinase 3 (TIMP 3) and its protein expression in giant cell tumors of bone (GCT), and to investigate the cause for loss of TIMP 3 protein and the relationship between promoter methylation of TIMP 3 gene and histological grading and recurrence of the tumor Methods TIMP 3 protein expression was detected by S P immunohistochemistry and Western blot TIMP 3 gene promoter methylation was detected by methylation specific PCR (MSP) Results TIMP 3 was expressed in the cytoplasm of mononuclear stromal cells and multinucleated giant cells The protein was expressed more stronger at one polar of multinucleated giant cells However, loss of TIMP 3 protein expression was found in 5 out 17 cases (29 4%) of GCT, in which 4 cases had TIMP 3 methylation and they were all grade II by histological grading Conclusions Bone absorption of GCT lesion may associate with the loss of TIMP 3 protein Methylation of TIMP 3 promoter is the most important mechanism for loss of TIMP 3 protein expression in giant cell tumor of bone