title: Differential expression of CKS-1B in typical and blastoid variants of mantle cell lymphoma.
abstract: Mantle cell lymphoma is a distinct type of B-cell lymphoma characterized by the t(11;14)(q13;q32). Mantle cell lymphomas exhibit a spectrum of morphologic findings, of which a subset of tumors is clinically aggressive with a high proliferation rate. These neoplasms are known as aggressive variants of which there are blastoid and pleomorphic subsets. CKS-1B (CDC28 protein kinase regulatory subunit 1B) is essential for the ubiquitination and degradation of p27 and cell cycle progression. We analyzed CKS-1B expression in mantle cell lymphoma cell lines and tumors by Western blot and immunohistochemical analysis. In 4 mantle cell lymphoma cell lines, CKS-1B was expressed at variable levels and correlated inversely with p27 expression. In mantle cell lymphoma tumors, CKS-1B was positive in 10 (28.6%) of 35 typical versus 14 (87.5%) of 16 blastoid/pleomorphic cases (Fisher exact test, P = .0002). Analyzed as a continuous variable, the percentage of CKS-1B-positive cells significantly correlated with blastoid/pleomorphic morphology (Mann-Whitney U test, P = .001). Twelve (23.5%) of 51 mantle cell lymphoma tumors expressed p27. Proliferation rate (Ki-67) was higher in blastoid/pleomorphic variants than in typical mantle cell lymphoma tumors and was inversely associated with p27 levels in typical mantle cell lymphoma. However, CKS-1B expression did not correlate with p27 expression, proliferation rate, or prognosis in the entire study group. Fluorescence in situ hybridization analysis of 10 CKS-1B-positive mantle cell lymphoma tumors showed no evidence of CKS-1B gene amplification. We conclude that CKS-1B is commonly expressed in mantle cell lymphoma, particularly in aggressive histologic variants, and may be involved in pathogenesis.
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Nalan
authors.initials: N
authors.lastname: Akyurek
authors.forename: Elias
authors.initials: E
authors.lastname: Drakos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Giaslakiotis
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Knoblock
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Yi
authors.initials: Y
authors.lastname: Ning
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism* / Q000473:pathology
chemical_list: C093090:CKS1B protein, human; D002352:Carrier Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases