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BCL-2 Expression Correlates With Lower Proliferative Activity in the Intermediate- and High-Grade Non-Hodgkin's Lymphomas: An Eastern Cooperative Oncology Group and Southwest Oncology Group Cooperative Laboratory Study

Jane N. Winter, Janet Andersen, John C. Reed, Stanislaw Krajewski, Daina Variakojis, Kenneth D. Bauer, Richard I. Fisher, Leo I. Gordon, Martin M. Oken, Shuwei Jiang, David Jeffries, and Peter Domer

From the Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL; The Burnham Institute, La Jolla, CA; Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL; The Virginia Piper Cancer Institute, Abbott-Northwestern Hospital, Minneapolis, MN; and the Eastern Cooperative Oncology Group Statistical Center, the Dana-Farber Cancer Institute, Boston, MA.

An inverse relationship between BCL-2 expression and cell cycle transition has been suggested by recent studies in murine models. To investigate the clinical relevance of these laboratory studies, a group of 116 paraffin-embedded non-Hodgkin's lymphoma (NHL) biopsy specimens (Working Formulation Groups D-H, and J) from a cooperative group study of cellular DNA content were analyzed for the 14;18 translocation using polymerase chain reaction (PCR)-based methods and, if sufficient tissue remained, for BCL-2 and BAX expression by immunohistochemistry. The results of these studies were then compared with the results of the previously performed flow cytometric analysis of ploidy and proliferative activity (S-phase-fraction). BCL-2 expression was inversely associated with proliferative activity (P = .001; n = 41), but there was no association between staining for Bax and %S-phase. Ploidy was not associated with either BCL-2 or BAX expression. The t(14;18) was detected in 21 of the 54 cases in which PCR-amplifiable DNA was recovered; 20 of these occurred at the major breakpoint region and 1 at the minor breakpoint region. High levels of BCL-2 or BAX expression occurred independently of t(14;18). There was no association between t(14;18) and either ploidy or proliferative activity. The inverse relationship between BCL-2 expression and proliferative activity in the intermediate- and high-grade NHLs is consistent with recent studies suggesting that Bcl-2 both retards entry into the cell cycle and inhibits apoptosis.

Blood, Vol. 91 No. 4 (February 15), 1998: pp. 1391-1398
© 1998 by The American Society of Hematology.


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