Expression of bcl2 family proteins and active caspase 3 in classical Hodgkin's lymphomas.
The expression of various bcl2 family proteins has been reported in Hodgkin and Reed-Sternberg cells, but the proteins bad, bid, and bim have not been analyzed in classical Hodgkin's lymphomas (HLs). This study aimed to investigate the expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, bim, and active caspase 3, and the TUNEL (terminal deoxynucleotidyl transferase-mediated in situ labeling) index to gain further insight into the apoptosis profile of classical HLs. A high expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, and bim in HRS cells was found in 27 of 101 (27%), 95 of 101 (94%), 27 of 97 (29%), 73 of 95 (77%), 37 of 102 (36%), 85 of 94 (90%), 19 of 109 (17%), and 43 of 91 (47%) cases, respectively. The high expression of bcl-xl, bax, and bad in HRS cells in most classical HLs indicates that these proteins may play predominant roles in the regulation of apoptosis in classical HLs. Active caspase 3-positive and TUNEL-positive Reed-Sternberg cells were detected in 47 of 70 (67%; range, 0%-12%) and 60 of 71 (85%; range, 0%-19%) cases, respectively. Significant positive correlations were found between bax/bcl2 (P = .002), bad/bcl2 (P = .020), bad/bcl-xl (P = .003), and bim/mcl1 (P = .036). Based on these findings, it could be hypothesized that the antiapoptotic proteins bcl2, bcl-xl, and mcl1 may counteract the expression of the proapoptotic proteins bax, bad, and bim, thereby contributing to the survival of Reed-Sternberg cells.
Bai
Maria
M
Department of Pathology, Medical Faculty, University of Ioannina, Ioannina 45110, Greece. mbai@cc.uoi.gr
Papoudou-Bai
Alexandra
A
Horianopoulos
Nikolaos
N
Grepi
Constantina
C
Agnantis
Niki John
NJ
Kanavaros
Panagiotis
P
D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000032:analysis; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000096:biosynthesis*; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000032:analysis; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D016539:Reed-Sternberg Cells / Q000737:chemistry / Q000473:pathology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis; D051025:bcl-Associated Death Protein / Q000032:analysis; D051020:bcl-X Protein / Q000032:analysis
D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C494772:BAK1 protein, human; C494826:BAX protein, human; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D053148:Caspase 3