PATHOGENETIC AND CLINICAL IMPLICATIONS OF BCL-6 AND BCL-2 GENE CONFIGURATION IN NODAL DIFFUSE LARGE B-CELL LYMPHOMAS

Bcl-6 (LAZ-3) and Bcl-2 gene rearrangements have been respectively rep orted in 20-35 per cent and 10-25 per cent of diffuse large B-cell lym phomas (DLBCLs), Although these genetic lesions have been associated w ith different clinical outcomes (i.e., more favourable in Bcl-6 rearra nged cases and poorer in Bcl-2 rearranged cases): their prognostic sig nificance is still controversial, In the present study, we have invest igated by Southern blot analysis the Bcl-6 and Bcl-2 gene configuratio n in a series of 80 lymph nodes involved by well-characterized DLBCLs, histologically defined according to the REAL and the updated Kiel cla ssifications, The molecular findings have been correlated with the cli nical features at presentation and with response to therapy, The major ity of cases (57/80=71.2 per cent) had a centroblastic morphology. Bcl -6 rearrangements were detected in 23/80 cases (28.8 per cent), and we re similarly associated with centroblastic (18/57=31.6 per cent) or im munoblastic (3/11=27.3 per cent) histotypes. In contrast, Bcl-2 was fo und to be rearranged in only three cases of centroblastic lymphoma (3. 8 per cent). No significant differences were found between Bcl-6 rearr anged and germline cases, as far as the clinical features at presentat ion are concerned, Forty-one patients, in whom the lymph node biopsy w as performed at diagnosis, could be evaluated for response to treatmen t and clinical outcome, Most of these cases (30/41=73.2 per cent) mere nodal DLBCL, without extranodal site involvement, Analysis of the cli nical outcome showed no statistically significant differences between Bcl-6 rearranged and Bcl-6 germline cases (actuarial overall survival 50 per cent vs, 48 per cent, event-free survival 45 per cent vs, 46 pe r cent, at 4 years), These findings confirm that Bcl-6 rearrangements are the most frequent genetic lesion in DLBCL, The incidence of Bcl-2 involvement in our series is significantly lower than the figures repo rted in other studies, mainly from North American countries, probably reflecting heterogeneous patient selection and/or epidemiological vari ability, Finally, our results suggest that no relevant clinical differ ences are observed between Bcl-6 rearranged and Bcl-6 germline cases, when nodal DLBCLs are considered. (C) 1997 John Wiley & Sons, Ltd.