Division of Hematopathology, Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Mod Pathol. 2011 Nov;24(11):1433-43. doi: 10.1038/modpathol.2011.103. Epub 2011 Jun 17.
Lymphoid-enhancer-binding factor 1 (LEF1), coupling with β-catenin, functions as a key nuclear mediator of WNT/β-catenin signaling, which regulates cell proliferation and survival. LEF1 has an important role in lymphopoiesis, and is normally expressed in T and pro-B cells but not mature B cells. However, gene expression profiling demonstrates overexpression of LEF1 in chronic lymphocytic leukemia, and knockdown of LEF1 decreases the survival of the leukemic cells. So far, the data on LEF1 expression in B-cell lymphomas are limited. This study represents the first attempt to assess LEF1 by immunohistochemistry in a large series (290 cases) of B-cell lymphomas. Strong nuclear staining of LEF1 was observed in virtually all neoplastic cells in 92 of 92 (100%) chronic lymphocytic leukemia/small lymphocytic lymphomas including two CD5- cases, with strongest staining in cells with Richter's transformation. LEF1 also highlighted the morphologically inconspicuous small lymphocytic lymphoma component in three composite lymphomas. All 53 mantle cell lymphomas, 31 low-grade follicular lymphomas and 31 marginal zone lymphomas, including 3 CD5+ cases, were negative. In 12 grade 3 follicular lymphomas, LEF1 was positive in a small subset (5-15%) of cells. Diffuse large B-cell lymphoma, however, demonstrated significant variability in LEF1 expression with overall positivity in 27 of 71 (38%) cases. Our results demonstrate that nuclear overexpression of LEF1 is highly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma, and may serve as a convenient marker for differential diagnosis of small B-cell lymphomas. The expression of β-catenin, the coactivator of LEF1 in WNT signaling, was examined in 50 chronic lymphocytic leukemia/small lymphocytic lymphomas, of which 44 (88%) showed negative nuclear staining. The findings of universal nuclear overexpression of LEF1 but lack of nuclear β-catenin in the majority of chronic lymphocytic leukemia/small lymphocytic lymphoma suggest that the pro-survival function of LEF1 in this disease may be independent of WNT/β-catenin signaling.
淋巴增强因子结合蛋白 1（LEF1）与β-连环蛋白结合，作为 WNT/β-连环蛋白信号转导的关键核介质发挥作用，该信号转导调节细胞增殖和存活。LEF1 在淋巴生成中起重要作用，正常表达于 T 和前 B 细胞，但不表达于成熟 B 细胞。然而，基因表达谱分析表明慢性淋巴细胞白血病中 LEF1 表达过度，LEF1 敲低可降低白血病细胞的存活。迄今为止，B 细胞淋巴瘤中 LEF1 表达的数据有限。本研究首次尝试通过免疫组化在 290 例 B 细胞淋巴瘤的大系列中评估 LEF1。在 92 例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（包括 2 例 CD5-病例）中，几乎所有肿瘤细胞均出现 LEF1 强核染色，在 Richter 转化细胞中染色最强。LEF1 还突出了三种复合淋巴瘤中形态上不明显的小淋巴细胞淋巴瘤成分。所有 53 例套细胞淋巴瘤、31 例低度滤泡性淋巴瘤和 31 例边缘区淋巴瘤（包括 3 例 CD5+病例）均为阴性。在 12 例 3 级滤泡性淋巴瘤中，LEF1 在一小部分（5-15%）细胞中呈阳性。弥漫性大 B 细胞淋巴瘤的 LEF1 表达存在显著差异，71 例中有 27 例（38%）阳性。我们的结果表明，LEF1 的核过表达与慢性淋巴细胞白血病/小淋巴细胞淋巴瘤高度相关，可能作为小 B 细胞淋巴瘤鉴别诊断的方便标志物。共激活物β-连环蛋白在 WNT 信号转导中的表达在 50 例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤中进行了检测，其中 44 例（88%）显示核阴性染色。在大多数慢性淋巴细胞白血病/小淋巴细胞淋巴瘤中，LEF1 普遍出现核过表达但缺乏核β-连环蛋白的发现表明，LEF1 在该疾病中的促生存功能可能独立于 WNT/β-连环蛋白信号转导。
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