Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mod Pathol. 2010 Mar;23(3):420-33. doi: 10.1038/modpathol.2009.173. Epub 2010 Jan 8.
D-cyclin proteins play a central role in cell-cycle regulation and are involved in the pathogenesis of lymphomas. In mantle-cell lymphoma, the t(11;14) translocation leads to overexpression of cyclin-D1, in addition to which cyclin-D1-negative mantle-cell lymphoma that overexpress cyclin-D2 or D3 have also been described. Although cyclin-D2 and D3 have been implicated in the prognosis of specific lymphoma subtypes, a thorough characterization of D-cyclin protein expression in human hematolymphoid neoplasia has not been reported. To evaluate the tissue expression patterns of D-cyclins, particularly D2 and D3, in normal and neoplastic hematolymphoid tissues, we optimized the commercially available antibodies for D-cyclins for use on paraffin-embedded tissue and stained tissue microarrays of over 700 patient samples. Our results show that cyclin-D2 and D3 proteins are expressed in many more lymphoma subtypes than cyclin-D1. Cyclin-D1, D2 and D3 were expressed in 100, 22 and 6% of mantle-cell lymphomas and 2, 49 and 20% of diffuse large B-cell lymphomas. Fluorescence in situ hybridization studies confirmed the presence of the CCND1/IGH translocation in the majority of mantle-cell lymphoma, but not in diffuse large B-cell lymphoma that expressed cyclin-D1 protein. In addition, a subset of follicular, marginal zone, lymphoplasmacytic, lymphoblastic, classical Hodgkin, mature T-cell and natural killer cell lymphomas and acute myeloid leukemias also expressed cyclin-D2 and D3. These data support the hypothesis that dysregulation of cell-cycle control by D-cyclins contribute to the pathogenesis of hematolymphoid neoplasia, and suggest a potential role for these proteins in the prognostic and therapeutic aspects of these diseases. For diagnostic purposes, however, the expression of D-cyclin proteins should be interpreted with caution in the subclassification of lymphoma types.
D 型细胞周期蛋白在细胞周期调控中起着核心作用，并参与淋巴瘤的发病机制。在套细胞淋巴瘤中，t（11;14）易位导致 cyclin-D1 的过表达，除此之外，还描述了 cyclin-D1 阴性套细胞淋巴瘤中 cyclin-D2 或 D3 的过表达。虽然 cyclin-D2 和 D3 已被牵连到特定淋巴瘤亚型的预后中，但 D 型细胞周期蛋白在人类血液淋巴肿瘤中的表达特征尚未得到全面描述。为了评估 D 型细胞周期蛋白，特别是 D2 和 D3，在正常和肿瘤性血液淋巴组织中的组织表达模式，我们优化了市售的 D 型细胞周期蛋白抗体，用于石蜡包埋组织，并对 700 多个患者样本的组织微阵列进行了染色。我们的结果表明，cyclin-D2 和 D3 蛋白在比 cyclin-D1 更多的淋巴瘤亚型中表达。cyclin-D1、D2 和 D3 在 100%、22%和 6%的套细胞淋巴瘤和 2%、49%和 20%的弥漫性大 B 细胞淋巴瘤中表达。荧光原位杂交研究证实，大多数套细胞淋巴瘤中存在 CCND1/IGH 易位，但在表达 cyclin-D1 蛋白的弥漫性大 B 细胞淋巴瘤中不存在。此外，滤泡性、边缘区、淋巴浆细胞性、淋巴母细胞性、经典霍奇金、成熟 T 细胞和自然杀伤细胞淋巴瘤和急性髓系白血病的亚组也表达 cyclin-D2 和 D3。这些数据支持这样一种假说，即 D 型细胞周期蛋白对细胞周期控制的失调导致血液淋巴肿瘤的发病机制，并表明这些蛋白在这些疾病的预后和治疗方面具有潜在作用。然而，出于诊断目的，在淋巴瘤类型的亚分类中，D 型细胞周期蛋白蛋白的表达应谨慎解释。
