Izban K F, Alkan S, Singleton T P, Hsi E D
Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
Arch Pathol Lab Med. 2000 Oct;124(10):1457-62. doi: 10.5858/2000-124-1457-MIAOTC.
Mantle cell lymphoma (MCL) is characterized by overexpression of cyclin D1, a G1 cyclin that participates in the control of cell cycle progression at the G1 to S phase transition. In addition to cyclin D1, other cell cycle regulatory molecules may be involved in the proliferation and progression of MCL. Mutation of p53, deletion of p16(INK4a), and loss of p21(WAF1) expression have been reported in some cases of blastoid MCL.
We sought to examine levels of expression of these proteins in typical and blastoid MCL and to determine whether differences were present between these subtypes of lymphomas.
A retrospective series of typical and blastoid MCLs was evaluated for expression of the cell cycle-related proteins cyclin D1, p21(WAF1), p27(KIP1), Ki-67, and p53, as well as mitotic index. Paraffin-embedded archival tissues from 24 MCL specimens (17 typical, 7 blastoid) were immunostained with antibodies to p21(WAF1), p27(KIP1), p53, Ki-67, and cyclin D1. The percentage of positive cells for each specimen was estimated by counting 1500 cells under oil immersion microscopy. Levels of antigen expression were compared for the typical and blastoid MCLs. The mitotic index was estimated using twenty 100x oil immersion fields (OIFs) for each specimen.
Cyclin D1 expression was seen in 22/24 specimens (92%). Blastoid MCLs were characterized by a significantly higher mean mitotic index (>20 mitoses/20 OIFs) and Ki-67 index (>45%) when compared with typical MCLs (P <.001 and P <.008, respectively; Fisher's exact test). High expression of p27(KIP1) (>25% staining) was seen more frequently in typical MCLs than in the blastoid variants (P =.03; Fisher's exact test). No significant differences were found between typical and blastoid MCLs for the expression of p21(WAF1) or p53.
A significantly higher mitotic index and Ki-67 index were found in blastoid MCLs as compared with typical MCLs. Low p27(KIP1) expression was associated with the blastoid MCL variant. These findings confirm the high proliferative nature of blastoid MCL and suggest a role for p27(KIP1) in the negative regulation of the cell cycle in MCL.
套细胞淋巴瘤（MCL）的特征是细胞周期蛋白D1过度表达，细胞周期蛋白D1是一种G1期细胞周期蛋白，参与细胞周期从G1期到S期转换的调控。除细胞周期蛋白D1外，其他细胞周期调节分子可能也参与MCL的增殖和进展。在一些母细胞样MCL病例中，已报道存在p53突变、p16（INK4a）缺失和p21（WAF1）表达缺失。
我们试图检测这些蛋白在典型和母细胞样MCL中的表达水平，并确定这些淋巴瘤亚型之间是否存在差异。
对一系列典型和母细胞样MCL进行回顾性评估，检测细胞周期相关蛋白细胞周期蛋白D1、p21（WAF1）、p27（KIP1）、Ki-67和p53的表达以及有丝分裂指数。用抗p21（WAF1）、p27（KIP1）、p53、Ki-67和细胞周期蛋白D1的抗体对24例MCL标本（17例典型，7例母细胞样）的石蜡包埋存档组织进行免疫染色。通过在油镜下计数1500个细胞来估计每个标本的阳性细胞百分比。比较典型和母细胞样MCL的抗原表达水平。使用每个标本的20个100倍油镜视野（OIF）估计有丝分裂指数。
22/24例标本（92%）可见细胞周期蛋白D1表达。与典型MCL相比，母细胞样MCL的平均有丝分裂指数（>20个有丝分裂/20个OIF）和Ki-67指数（>45%）显著更高（分别为P<.001和P<.008；Fisher精确检验）。典型MCL中p27（KIP1）高表达（>25%染色）比母细胞样变体更常见（P=.03；Fisher精确检验）。典型和母细胞样MCL在p21（WAF1）或p53表达上未发现显著差异。
与典型MCL相比，母细胞样MCL的有丝分裂指数和Ki-67指数显著更高。p27（KIP1）低表达与母细胞样MCL变体相关。这些发现证实了母细胞样MCL的高增殖特性，并提示p27（KIP1）在MCL细胞周期的负调控中起作用。
