PROGNOSTIC-SIGNIFICANCE OF BCL-2 PROTEIN EXPRESSION IN AGGRESSIVE NON-HODGKINS-LYMPHOMA

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and progn ostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or in termediate grade NHL. These patients were uniformly treated with adria mycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were e xcluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in vir tually all tumor cells, whereas 65 (23%) were negative and 94 (32%) ex hibited 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 histol ogical subtypes. Further analysis was performed on the 151 patients wi th 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 immuno-histological subgroup. High bcl-2 expression, found in 44% of these patients (67 o f 151), was more frequently associated with III-IV stage disease (P =. 002). Reduced disease-free survival (DFS) (P <.01) and overall surviva l (P <.05) were demonstrated in the patients with high bcl-2 expressio n. Indeed, the 3-year estimates of DFS and overall survival were 60% a nd 61%, respectively (high bcl-2 expression) versus 82% and 78%, respe ctively (negative/intermediate bcl-2 expression). A multivariate regre ssion analysis confirmed the independent effect of bcl-2 protein expre ssion on DFS. Thus bcl-2 protein expression, as demonstrated in routin ely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. i t might be considered as a new independent biologic prognostic paramet er, which, especially in diffuse large B-cell NHL, could aid in the id entification of patient risk groups. (C) 1996 by The American Society of Hematology.