Expression of p34(cdc2) and cyclins A and B compared to other proliferative features of non-Hodgkin's lymphomas: a multivariate cluster analysis.
In view of recent knowledge on proteins regulating the cell cycle, we re-evaluated proliferative features of 98 diffusely growing non-Hodgkin's lymphomas. The combined use of 5 proliferation-associated variables (mitotic indices and percentages of Ki-67(+), p34(cdc2+), cyclin A(+) and cyclin B(+) cells) and their entry into a multivariate cluster analysis separated, without overlaps, the entire cohort into 3 groups (clusters) with (1) low, (2) intermediate and (3) high proliferative activity. Conversely, bivariate plots exposed considerable cluster overlaps. Multivariate stepwise discriminant analysis of all cases revealed a decreasing order of discriminant power for % Ki-67(+) cells > % p34(cdc2+) cells > mitotic index > % cyclin A(+) cells > % cyclin B(+) cells. The combined use of 2 variables only, mitotic index and % p34(cdc2+) cells, allowed a clear-cut separation of clusters 2 and 3. In bivariate plots, correlations were best between % Ki-67(+) cells and % cyclin A(+) cells and between mitotic indices and % cyclin B(+) cells. Except for chronic lymphocytic leukemias, immunocytomas and marginal zone lymphomas (all in cluster 1), individual lymphoma entities were distributed among at least 2 clusters. There was, however, a marked preponderance of mantle cell lymphomas and diffuse follicular center lymphomas in cluster 1 and of diffuse large B-cell lymphomas and peripheral T-cell lymphomas in cluster 2. Anaplastic large-cell lymphomas predominated in cluster 3 and responded best to therapy.
Leoncini
L
L
Institute of Pathology, University of Sassari, Sassari, Italy. leoncinil@unisi.it
Cossu
A
A
Megha
T
T
Bellan
C
C
Lazzi
S
S
Luzi
P
P
Tosi
P
P
Barbini
P
P
Cevenini
G
G
Pileri
S
S
Giordano
A
A
Kraft
R
R
Laissue
J A
JA
Cottier
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016203:CDC2 Protein Kinase / Q000096:biosynthesis* / Q000502:physiology; D002455:Cell Division; D002648:Child; D016000:Cluster Analysis; D015331:Cohort Studies; D019925:Cyclin A / Q000096:biosynthesis* / Q000502:physiology; D019926:Cyclin B / Q000096:biosynthesis* / Q000502:physiology; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies
D019925:Cyclin A; D019926:Cyclin B; D016203:CDC2 Protein Kinase