title: Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.
abstract: The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10+/-/MUM1-/CD138-: 29 cases and bcl6-/CD10+/MUM1-/CD138-: two cases) and the nongerminal center B-cell-like profile (bcl6+/-/CD10-/MUM1+/CD138-); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=-0.536, P<0.001 and r=-0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=-0.276, P=0.014) and bid (r=-0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.
authors.affiliation: Department of Pathology, Medical Faculty, University of Ioannina, Ioannina, Greece. mbai@cc.uoi.gr
authors.forename: Maria
authors.initials: M
authors.lastname: Bai
authors.forename: Angelos
authors.initials: A
authors.lastname: Skyrlas
authors.forename: Niki John
authors.initials: NJ
authors.lastname: Agnantis
authors.forename: Sevasti
authors.initials: S
authors.lastname: Kamina
authors.forename: Elena
authors.initials: E
authors.lastname: Tsanou
authors.forename: Constantina
authors.initials: C
authors.lastname: Grepi
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Galani
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kanavaros
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D016009:Chi-Square Distribution; D004268:DNA-Binding Proteins / Q000032:analysis; D018858:Germinal Center / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D050835:Interferon Regulatory Factors; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000032:analysis; D015260:Neprilysin / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000099218:Interferon Regulatory Factor-4
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D008565:Membrane Proteins; D015260:Neprilysin; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000099218:Interferon Regulatory Factor-4; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C494814:BID protein, human