Swerdlow S H, Yang W I, Zukerberg L R, Harris N L, Arnold A, Williams M E
Department of Pathology, University of Pittsburgh School of Medicine, PA, USA.
Hum Pathol. 1995 Sep;26(9):999-1004. doi: 10.1016/0046-8177(95)90090-x.
Centrocytic/mantle cell lymphoma (CC/MCL) is a morphologically defined B-cell non-Hodgkin's lymphoma characterized by a distinctive immunophenotype, BCL1/cyclin D1 (PRAD1) gene rearrangements, and, most recently, by overexpression of cyclin D1. Even using multiple breakpoint probes for BCL1 (MTC, p94PS) and cyclin D1, however, only approximately 70% of CC/MCL have a rearrangement consistent with a t(11;14) (q13;q32). To determine whether the type of molecular translocation affects the degree of cyclin D1 expression and to evaluate lymphomas diagnosed as CC/MCL but lacking molecular evidence of a BCL1 or cyclin D1 translocation, 16 CC/MCL and four cases of small lymphocytic lymphoma/B-CL1 (SLL/B-CLL) were stained using an anti-cyclin D1 antibody. All cases with a cyclin D1 translocation detected by Southern blotting techniques as well as four of the five CC/MCL without a documentable translocation showed nuclear cyclin D1 protein expression. There was no apparent correlation between staining intensity and the precise site or presence of a detectable translocation. Cases with a mantle zone growth pattern showed infiltration of the cyclin D1 positive cells into reactive follicular centers. None of the four SLL/B-CLL showed cyclin D1 expression. These findings show overexpression of the cyclin D1 protein in virtually all CC/MCL independent of the type or presence of a documentable BCL1 or cyclin D1 molecular rearrangement. The mechanism for cyclin D1 overexpression in the cases without a documentable rearrangement and the relationship of cyclin D1 overexpression to the pathogenesis of mantle cell neoplasia remain uncertain.
中心细胞性/套细胞淋巴瘤(CC/MCL)是一种形态学定义的B细胞非霍奇金淋巴瘤,其特征为独特的免疫表型、BCL1/细胞周期蛋白D1(PRAD1)基因重排,以及最近发现的细胞周期蛋白D1过表达。然而,即使使用针对BCL1(MTC,p94PS)和细胞周期蛋白D1的多个断点探针,也只有约70%的CC/MCL具有与t(11;14)(q13;q32)一致的重排。为了确定分子易位类型是否影响细胞周期蛋白D1的表达程度,并评估诊断为CC/MCL但缺乏BCL1或细胞周期蛋白D1易位分子证据的淋巴瘤,使用抗细胞周期蛋白D1抗体对16例CC/MCL和4例小淋巴细胞淋巴瘤/B细胞慢性淋巴细胞白血病(SLL/B-CLL)进行染色。所有通过Southern印迹技术检测到细胞周期蛋白D1易位的病例,以及5例无明确易位的CC/MCL中的4例,均显示细胞核细胞周期蛋白D1蛋白表达。染色强度与可检测易位的精确位点或存在之间没有明显相关性。具有套区生长模式的病例显示细胞周期蛋白D1阳性细胞浸润到反应性滤泡中心。4例SLL/B-CLL均未显示细胞周期蛋白D1表达。这些发现表明,几乎所有CC/MCL中细胞周期蛋白D1蛋白均过表达,与可记录的BCL1或细胞周期蛋白D1分子重排的类型或存在无关。无明确重排病例中细胞周期蛋白D1过表达的机制以及细胞周期蛋白D1过表达与套细胞肿瘤发生机制的关系仍不确定。