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

Aims: To examine the expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x, Bcl-x(L) 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). Methods and 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-x(L) 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 greater than or equal to 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-x(L) showed an inverse correlation with apoptosis in the H/RS cells (P = 0.004). Conclusions: The higher Bcl-x(L) expression (67.2%) compared with Bcl-2 expression (43.5%) observed in cHL as well as the statistically significant inverse relationship between Bcl-x(L) and apoptosis suggests that Bcl-x(L) 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-x(L).