Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degr
ee of morphologic and clinical heterogeneity. We studied 156 patients
with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncoge
nes by Southern blot analysis and BCL2 protein expression. We related
these data to the primary site of presentation, disease stage, and oth
er clinical risk factors. Structural alterations of BCL2, BCL6, and MY
C were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respe
ctively. Three cases showed a combination of BCL2 and BCL6 rearrangeme
nts, and two cases had a combination of BCL6 and MYC rearrangements. B
CL2 rearrangement was found more often in extensive (39%) and primary
nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 r
earrangement was present in none of 40 patients with stage I disease,
but in 22% of patients with stage II to IV (P = .006). The presence of
BCL2 rearrangements did not significantly affect overall survival (OS
) or disease-free survival (DFS). In contrast, high BCL2 protein expre
ssion adversely affected both OS (P = .008) and DFS (P = .01). BCL2 pr
otein expression was poorly correlated with BCL2 rearrangement: only 5
2% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had
high BCL2 protein expression. Rearrangement of BCL6 was found more of
ten in patients with extranodal (36%) and extensive (39%) presentation
versus primary nodal disease (28%). No significant correlation was fo
und with disease stage, lymphadenopathy, or bone marrow involvement. D
FS and OS were not influenced by BCL6 rearrangements. MYC rearrangemen
ts were found in 16% of primary extranodal lymphomas, versus 2% of pri
mary nodal cases (P = .02). In particular, gastrointestinal (GI) lymph
omas (5 of 18 cases, 28%) were affected by MYC rearrangements, The dis
tinct biologic behavior of these extranodal lymphomas was reflected by
a high complete remission (CR) rate: 7 of 10 patients with MYC rearra
ngement attained complete remission and 6 responders remained alive fo
r more than 4 years, resulting in a trend for better DFS (P = .07). Th
ese data show the complex nature of molecular events in DLCL, which is
a reflection of the morphologic and clinical heterogeneity of these l
ymphomas. However, thus far, these genetic rearrangements fail as prog
nostic markers. (C) 1998 by The American Society of Hematology.