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Prognostic significance of bcl-2 protein expression in aggressive non-
Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)
O Hermine, C Haioun, E Lepage, MF d'Agay, J Briere, C Lavignac, G Fillet, G Salles, JP Marolleau, J Diebold, F Reyas and P Gaulard
Departement de Pathologie, Hopital Henri Mondor, Creteil, France.
Little is known about the expression of bcl-2 protein in intermediate and
high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic
significance. We performed immunohistochemical analysis of bcl-2 expression
in tumoral tissue sections of 348 patients with high or intermediate grade
NHL. These patients were uniformly treated with adriamycin,
cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the
induction phase of the LNH87 protocol. Fifty eight cases were excluded due
to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed
homogeneous positivity (high bcl-2 expression) in virtually all tumor
cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate
staining. High bcl-2 expression was more frequent in B-cell NHL (109 of
214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was
heterogeneously distributed among the different histological subtypes.
Further analysis was performed on the 151 patients with diffuse large
B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical
significance and potential prognostic value of bcl-2 expression in the most
frequent and homogeneous immunohistological subgroup. High bcl-2
expression, found in 44% of these patients (67 of 151), was more frequently
associated with III-IV stage disease (P = .002). Reduced disease-free
survival (DFS) (P < .01) and overall survival (P < .05) were
demonstrated in the patients with high bcl-2 expression. Indeed, the 3-
year estimates of DFS and overall survival were 60% and 61%, respectively
(high bcl-2 expression) versus 82% and 78%, respectively
(negative/intermediate bcl-2 expression). A multivariate regression
analysis confirmed the independent effect of bcl-2 protein expression on
DFS. Thus bcl-2 protein expression, as demonstrated in routinely
paraffin-embedded tissue, appears to be predictive of poor DFS, in
agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It
might be considered as a new independent biologic prognostic parameter,
which, especially in diffuse large B-cell NHL, could aid in the
identification of patient risk groups.
Volume 87,
Issue 1,
pp. 265-272,
01/01/1996
Copyright © 1996 by The American Society of Hematology
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