Cortactin expression in non-Hodgkin B-cell lymphomas: a new marker for the differential diagnosis between chronic lymphocytic leukemia and mantle cell lymphoma

Summary 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.