title: Expression of Mcl-1 in mantle cell lymphoma is associated with high-grade morphology, a high proliferative state, and p53 overexpression.
abstract: Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin's lymphoma characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. Defects in apoptosis may contribute to pathogenesis. This study evaluated the expression of the anti-apoptotic protein Mcl-1 in two MCL cell lines and five frozen MCL tumours (four small-cell, one blastoid/large-cell) using western blot analysis. Mcl-1 expression was also assessed in 36 formalin-fixed, paraffin wax-embedded MCL tumours (24 small-cell, 12 blastoid/large-cell) by immunohistochemistry. Western blot analysis revealed the expected 37 kD protein product in both MCL cell lines and in five frozen tumours, with the blastoid case having the highest expression level. Using a cut-off of >10% immunolabelled cells for Mcl-1, it was found that 12 of 36 MCL tumours were positive. Mcl-1-positive tumours had a higher frequency of blastoid/large-cell morphology (8/12 versus 4/24, p = 0.009), p53 overexpression (3/10 versus 1/23, p = 0.04), and higher Ki67 immuno-labelling (p = 0.002). It is concluded that expression of Mcl-1 in MCL is heterogeneous. A relatively high level of Mcl-1 expression correlates with high-grade morphology, a high proliferative state, and p53 overexpression.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Khoury
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: George Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonnell
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D002455:Cell Division / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53