Kauzman Adel, Li Shu Qiu, Bradley Grace, Bell Robert S, Wunder Jay S, Kandel Rita
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1x5, Canada.
Mod Pathol. 2003 Mar;16(3):210-8. doi: 10.1097/01.MP.0000057235.65327.40.
Cyclins play an important role in regulating the passage of dividing cells through critical checkpoints in the cell cycle. Because alterations of several cyclins, especially cyclin D1, have been implicated in the development of many human neoplasms, we examined 32 cases of giant cell tumor of long bones for cyclin D1 gene amplification and protein overexpression using differential polymerase chain reaction and immunohistochemistry, respectively. In addition, the expression of cyclin D3, cyclin B1, and the proliferation-associated antigen Ki-67 (MIB-1) was assessed immunohistochemically. Low-level cyclin D1 gene amplification was detected in 61% of giant cell tumor cases. All tumors showed cyclin D1, cyclin D3, cyclin B1, and Ki-67 (MIB-1) staining; however, the distribution was very characteristic. Cyclin D1 protein expression was seen predominantly in the nuclei of the giant cells, with occasional mononuclear cells staining. There was no correlation between cyclin D1 gene amplification and protein overexpression. Cyclin D3 staining showed a similar distribution, with 88% of cases showing protein overexpression. Cyclin D1 and/or D3 staining in the giant cells was never associated with staining for either cyclin B1 or Ki-67 (MIB-1), as the expression of the latter two proteins was restricted to the mononuclear cells. Cyclin B1 overexpression was seen in 44% of cases. Ki-67 (MIB-1) staining was present in all cases, and between 10 to 50% of the mononuclear cells were positive. These results suggest that alterations in cyclin D1 and/or D3 might play a role in the pathogenesis of giant cell tumor of bone.
细胞周期蛋白在调节分裂细胞通过细胞周期中的关键检查点方面发挥着重要作用。由于几种细胞周期蛋白的改变，尤其是细胞周期蛋白D1，与许多人类肿瘤的发生有关，我们分别使用差异聚合酶链反应和免疫组织化学方法，检测了32例长骨巨细胞瘤中的细胞周期蛋白D1基因扩增和蛋白过表达情况。此外，还通过免疫组织化学方法评估了细胞周期蛋白D3、细胞周期蛋白B1以及增殖相关抗原Ki-67（MIB-1）的表达。在61%的巨细胞瘤病例中检测到低水平的细胞周期蛋白D1基因扩增。所有肿瘤均显示细胞周期蛋白D1、细胞周期蛋白D3、细胞周期蛋白B1和Ki-67（MIB-1）染色；然而，其分布非常具有特征性。细胞周期蛋白D1蛋白表达主要见于巨细胞的细胞核，偶尔有单核细胞染色。细胞周期蛋白D1基因扩增与蛋白过表达之间无相关性。细胞周期蛋白D3染色显示类似的分布，88%的病例显示蛋白过表达。巨细胞中的细胞周期蛋白D1和/或D3染色从未与细胞周期蛋白B1或Ki-67（MIB-1）的染色相关，因为后两种蛋白的表达仅限于单核细胞。44%的病例出现细胞周期蛋白B1过表达。所有病例均有Ki-67（MIB-1）染色，10%至50%的单核细胞呈阳性。这些结果表明，细胞周期蛋白D1和/或D3的改变可能在骨巨细胞瘤的发病机制中起作用。
