Aguilera N S, Bijwaard K E, Duncan B, Krafft A E, Chu W S, Abbondanzo S L, Lichy J H, Taubenberger J K
Department of Hematologic and lymphatic Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Am J Pathol. 1998 Dec;153(6):1969-76. doi: 10.1016/s0002-9440(10)65710-0.
Mantle-cell lymphomas are associated with a characteristic chromosomal translocation, t(11;14)(q13;q32). This translocation involves rearrangement of the bcl-1 proto-oncogene from chromosome 11 to the immunoglobulin heavy chain gene on chromosome 14, resulting in an overexpression of cyclin D1 mRNA (also known as bcl-1 and PRAD1). In the current study performed on paraffin-embedded tissue, cyclin D1 mRNA could be detected in 23 of 24 mantle-cell lymphomas by reverse transcription polymerase chain reaction (RT-PCR) whereas only 9 of 24 demonstrated a t(11;14) by PCR. However, we also found that cyclin D1 mRNA could be detected in the majority (11 of 17, 65%) of non-mantle-cell lymphomas and in a minority of atypical lymphoid hyperplasias (3 of 7, 43%). Cyclin D1 mRNA expression was not observed in floridly reactive lymph nodes (0 of 9) or in unstimulated lymph nodes (0 of 20), suggesting that it is a sensitive adjunct marker for malignant lymphoproliferative processes, but not specific for mantle-cell lymphoma. A semiquantitative RT-PCR assay was developed that compared the ratio of cyclin D1 to the constitutively expressed gene beta2-microglobulin. Using this assay on a limited number of our specimens, cyclin D1 overexpression in mantle-cell lymphoma could be reliably distinguished from its expression in other non-Hodgkin's lymphomas. This assay for cyclin D1 expression, designed for formalin-fixed, paraffin-embedded tissue, was a very sensitive and specific marker for mantle-cell lymphoma.
套细胞淋巴瘤与一种特征性的染色体易位t(11;14)(q13;q32)相关。这种易位涉及bcl-1原癌基因从11号染色体重排至14号染色体上的免疫球蛋白重链基因，导致细胞周期蛋白D1 mRNA（也称为bcl-1和PRAD1）过度表达。在对石蜡包埋组织进行的当前研究中，通过逆转录聚合酶链反应（RT-PCR）在24例套细胞淋巴瘤中的23例中可检测到细胞周期蛋白D1 mRNA，而通过PCR仅在24例中的9例显示有t(11;14)。然而，我们还发现细胞周期蛋白D1 mRNA可在大多数（17例中的11例，65%）非套细胞淋巴瘤以及少数非典型淋巴样增生（7例中的3例，43%）中检测到。在活跃反应性淋巴结（9例中的0例）或未受刺激的淋巴结（20例中的0例）中未观察到细胞周期蛋白D1 mRNA表达，这表明它是恶性淋巴增殖性过程的敏感辅助标志物，但并非套细胞淋巴瘤所特有。开发了一种半定量RT-PCR检测方法，可比较细胞周期蛋白D1与组成性表达基因β2-微球蛋白的比例。在我们有限数量的标本上使用该检测方法，套细胞淋巴瘤中细胞周期蛋白D1的过表达可与其他非霍奇金淋巴瘤中的表达可靠区分开来。这种针对福尔马林固定、石蜡包埋组织设计的细胞周期蛋白D1表达检测方法，是套细胞淋巴瘤非常敏感且特异的标志物。
