Figure 5.

Hierarchical clustering analysis of Emi1, proliferation control, and mitotic control proteins in human tumors. For each tumor type, immunopositivity for Emi1, proliferation control (cyclins D1, D2, E, and A; β-catenin; p27^Kip1; Bcl2; and Ki67), and mitotic control/APC/C (aurora A, Plk1, securin, Cdh1, and Skp2) substrates were identified. Dendrograms for neural tumor (A) and lymphoma (B) TMAs are shown. Green rectangles indicate a tumor showing no immunopositivity, dark red indicates moderate positivity (3 to 29% of tumor cells positive), and bright red indicates high positivity (>30% tumor cells positive). Gray rectangles indicate unscorable TMA cores. The dendograms on the top horizontal axes show clusters of proliferation control proteins and APC/C substrate proteins. Oncogenic APC/C substrates securin, aurora A, Plk1, and Skp2 (red) form a cluster with Emi1 distinct from broader proliferation markers such as Ki67, cyclin A, and Bcl-2 in malignant neural tumors and lymphomas. The pink rectangles on the right vertical axes represent Emi1-positive tumors, which are largely malignant and positive for both proliferation and APC/C clusters. The yellow rectangles indicate mostly malignant tumors that are largely proliferation and APC/C cluster positive but Emi1 negative. The blue rectangles represent mostly benign or low-grade tumors that are predominantly proliferation cluster positive and APC/C cluster negative. ALCL, anaplastic large cell lymphoma; DLBCL, diffuse large B-cell lymphoma; FL1–3, follicular lymphoma grades 1 through 3; NKC, natural killer cell (lymphoma); NLP, nodular lymphocyte predominant Hodgkin’s lymphoma; CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; PTLD, posttransplant lymphoproliferative disorder.