Immunohistochemical analysis of p27^Kip1, Skp2, and Ki-67 expression in reactive lymphoid tissues and malignant lymphoma.

(A) Follicular hyperplasia. Reactive lymph nodes (p27^Kip1and Skp2). Expression of p27^Kip1 is present in quiescent cells of the follicular mantle zones and interfollicular T lymphocytes. Scattered germinal center centroblasts and interfollicular immunoblasts express Skp2. This staining pattern is similar to that of Ki-67 (data not shown). (B) Chronic lymphocytic leukemia (CLL)/SLL (hematoxylin and eosin [H&E] staining of p27^Kip1, Skp2, and Ki-67). Skp2 and Ki-67 expression highlights prolymphocytes and proliferation centers. (C) FCL (H&E staining of p27^Kip1, Skp2, and Ki-67). A section of low-grade FCL shows intense diffuse reactivity for p27^Kip1 in neoplastic and reactive lymphoid cells. Only scattered germinal center cells express Skp2 and Ki-67 relative to p27^Kip1. (D) MCL (H&E staining of p27^Kip1, Skp2, and Ki-67). Scattered tumor cells show similar levels of Skp2, p27^Kip1, and Ki-67 expression. (E) DLBCL (H&E staining of p27^Kip1, Skp2, and Ki-67). Section of intermediate-grade DLBCL shows scattered tumor cells expressing p27^Kip1. High levels of Skp2 and Ki-67 expression are seen in DLBCLs. The results show that the expression of Skp2 mirrors that of the proliferation marker Ki-67. (F) Double immunohistochemistry confirms the findings of single-immunolabeling studies. (Reactive lymph nodes shown for SLL/CLL, MZL, DLBCL.) Skp2⁺cells within proliferating germinal centers of a reactive lymph node are highlighted by the use of pink, whereas the p27^Kip1-positive cells within the mantle zones are brown. In a case of SLL/CLL, Skp2⁺ cells (pink) highlight proliferating immunoblasts within the pseudo-proliferation growth centers. Most of the small neoplastic lymphocytes of SLL/CLL are p27^Kip1 positive (brown). In MZL, Skp2⁺ cells (pink) highlight large centroblasts within a colonized follicle, whereas the surrounding small neoplastic and reactive lymphocytes are p27^Kip1 positive (brown). A DLBCL with a high proliferative index shows many Skp2⁺ cells (pink), with only scattered small reactive lymphocytes and endothelial cells that express p27^Kip1 (brown). Original magnification A, ×100; B-F, ×200.