Expression of Bcl-2 family members and presence of Epstein-Barr virus in the regulation of cell growth and death in classical Hodgkin's lymphoma.
OBJECTIVE
To examine the expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x, Bcl-xL and Bax) in classical Hodgkin's lymphoma (cHL) and to correlate the expression of these proteins with proliferation, apoptosis and the presence of Epstein-Barr virus (EBV).


RESULTS
Expression of the Bcl-2 family of proteins was detected by immunohistochemistry, proliferation was determined by Ki67 labelling and apoptosis by TUNEL in-situ hybridization. EBV was detected by Epstein-Barr virus early RNA (EBER) in-situ hybridization. Expression of Bcl-2, Bcl-x, Bcl-xL and Bax was detected in the Hodgkin/Reed-Sternberg (H/RS) cells in 43.7% (27/62), 87.5% (56/64), 67.2% (41/61) and 74.6% (47/63) of the cHL cases, respectively. EBER was detected in 53% (35/66) of the cases, whereas Ki67 was observed in 86.7% (52/60) of the cases. Apoptotic H/RS cells were observed infrequently, and only 43.2% (11/26) of the cases showed an apoptotic index of > or = 10% in the H/RS cells. A statistically significant inverse relationship was observed between the expression of Bcl-2 and the presence of EBV (P = 0.003). Bcl-xL showed an inverse correlation with apoptosis in the H/RS cells (P = 0.004).


CONCLUSIONS
The higher Bcl-xL expression (67.2%) compared with Bcl-2 expression (43.5%) observed in cHL as well as the statistically significant inverse relationship between Bcl-xL and apoptosis suggests that Bcl-xL plays an important role in the survival of H/RS cells. Expression of Bax may be neutralized by other anti-apoptotic members of the family such as Bcl-2 and/or Bcl-xL.
Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
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Kim
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Nadarajah
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Peh
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Poppema
D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis; D016923:Cell Death; D002455:Cell Division; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012269:Ribosomal Proteins / Q000096:biosynthesis; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D015703:Antigens, CD; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C067169:RPL22 protein, human