4 research outputs found
Expression of cyclin D3 and cyclin E and identification of distinct clusters of proliferation and apoptosis in diffuse large B-cell lymphomas
In the present study 79 cases of de novo
Diffuse Large B-cell Lymphomas (DLBCL) were
studied in order: a) to analyse the expression of cyclin
D3, cyclin E and cyclin D1 in relation to other
proliferative features (expression of Ki67, cyclin A and
cyclin B1), the apoptosis status and the expression of
p53, Rb, p16 and p27; and b) to determine whether
distinct clusters of proliferation and apoptosis could be
identified in DLBCL. Overexpression of cyclin D3 and
cyclin E was found in 35/79 (43%) and 18/79 (22%)
cases, respectively, whereas overexpression of cyclin D1
was not detected in any case. In most cases (39/46)
overexpression of cyclin D3 and cyclin E was mutually
exclusive possibly reflecting different underlying
pathways inducing deregulated expression of these
cyclins. In most cases (29/35) overexpression of cyclin
D3 was mutually exclusive with Rb/p16 aberrant
expression status supporting an oncogenic role for cyclin
D3 and suggesting that the pathogenetic effect of cyclin
D3 overexpression occurs through perturbation of the
Rb1 pathway. Combined alterations of the P53 and the
Rb/p16/cyclin D3 expression status were significantly
associated with higher mean values of cyclin A
(p=0.023) and cyclin B1 (p=0.033) indicating that
concurrent impairment of the p53 and Rb1 pathways
induces increased tumour cell proliferation in DLBCL.
Cluster analysis of the apoptosis and the proliferation
status permitted separation of DLBCL into distinct
groups with low (44 cases) and high (18 cases) apoptotic
activity and into distinct groups with low (32 cases),
intermediate (36 cases) and high (11 cases) proliferative
activity. The identification of distinct clusters with
respect to the proliferation and the apoptosis status
indicates that groups with distinct cellular kinetic
properties can be defined in the histological group of
DLBCL