General Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, 35121 Italy.
Hematology and Clinical Immunology Unit, Department of Medicine-DIMED, University of Padova, Padova, 35128 Italy.
Hum Pathol. 2019 Mar;85:251-259. doi: 10.1016/j.humpath.2018.10.038. Epub 2018 Nov 17.
Cortactin is a cytoskeletal-remodeling adaptor protein, playing an oncogenic role in solid tumors. Little is known on cortactin expression in non-Hodgkin B-cell lymphomas (B-NHLs). The present study aimed to characterize cortactin expression in B-NHLs and to assess its role in the differential diagnosis of such entities. Cortactin protein expression was first assessed by immunohistochemistry in a series of 131 B-NHLs, including B-cell chronic lymphocytic leukemia (CLL; n = 17), mantle cell lymphoma (MCL; n = 16), follicular lymphoma (FL; n = 25), marginal zone lymphoma (MZL; n = 30), hairy cell leukemia (HCL; n = 10), splenic diffuse red pulp small B-cell lymphomas (SDRPBL; n = 3), and diffuse large B-cell lymphoma (DLBCL; n = 30) cases. Cortactin was expressed in 14 of 17 CLLs, 10 of 10 HCLs, and 22 of 30 DLBCLs. MCLs, SDRPBLs, most FLs, and MZLs were cortactin negative. The immunohistochemical results were in keeping with in silico gene expression data. In CLL, cortactin positivity did correlate with LEF1 and CD200 expression, and the combined positivity for ≥2 markers strongly predicted CLL diagnosis. Such preliminary data suggested a role for cortactin in the differential diagnosis between CLL and MCL. This hypothesis was confirmed in a large validation set of 112 CLLs (n = 55) and MCLs (n = 57), which also disclosed rare cortactin-expressing MCLs. The immunohistochemical and gene expression results were sustained by flow cytometry and Western blot analysis on CLL and MCL cell lines. In conclusion, cortactin is mainly expressed in subsets of CLL and DLBCL and in HCL. Cortactin may represent a novel marker for the differential diagnosis between CLL and MCL.
Cortactin 是一种细胞骨架重塑衔接蛋白，在实体瘤中发挥致癌作用。关于非霍奇金 B 细胞淋巴瘤（B-NHL）中 cortactin 的表达知之甚少。本研究旨在研究 cortactin 在 B-NHL 中的表达，并评估其在这些实体的鉴别诊断中的作用。首先通过免疫组织化学法在 131 例 B-NHL 中检测 cortactin 蛋白的表达，包括 B 细胞慢性淋巴细胞白血病（CLL；n = 17）、套细胞淋巴瘤（MCL；n = 16）、滤泡性淋巴瘤（FL；n = 25）、边缘区淋巴瘤（MZL；n = 30）、毛细胞白血病（HCL；n = 10）、脾弥漫性红髓小 B 细胞淋巴瘤（SDRPBL；n = 3）和弥漫性大 B 细胞淋巴瘤（DLBCL；n = 30）。在 17 例 CLL 中有 14 例表达 cortactin，在 10 例 HCL 中有 10 例表达 cortactin，在 30 例 DLBCL 中有 22 例表达 cortactin。MCL、SDRPBL、大多数 FL 和 MZL 均为 cortactin 阴性。免疫组织化学结果与基因表达数据一致。在 CLL 中，cortactin 阳性与 LEF1 和 CD200 的表达相关，同时表达≥2 个标志物强烈提示 CLL 诊断。这些初步数据表明 cortactin 在 CLL 和 MCL 之间的鉴别诊断中起作用。在包含 112 例 CLL（n = 55）和 MCL（n = 57）的大型验证集中证实了这一假设，该研究还揭示了少数表达 cortactin 的 MCL。免疫组织化学和基因表达结果通过 CLL 和 MCL 细胞系的流式细胞术和 Western blot 分析得到证实。总之，cortactin 主要在 CLL 和 DLBCL 和 HCL 的某些亚群中表达。Cortactin 可能是 CLL 和 MCL 之间鉴别诊断的新标志物。
