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-ev aluated proliferative features of 98 diffusely growing non-Hodgkin's lympho mas. The combined use of 5 proliferation-associated variables (mitotic indi ces and percentages of Ki-67(+), p34(cdc2+), cyclin A(+) and cyclin B+ cell s) and their entry into a multivariate cluster analysis separated, without overlaps, the entire cohort into 3 groups (clusters) with (I) low, (2) inte rmediate and (3) high proliferative activity, Conversely, bivariate plots e xposed considerable cluster overlaps. Multivariate stepwise discriminant an alysis 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 an d % p34(cdc2+) cells, allowed a clear-cut separation of clusters 2 and 3. I n bivariate plots, correlations were best between % Ki-67(+) cells and % cy clin A(+) cells and between mitotic indices and % cyclin B+ cells. Except f or chronic lymphocytic leukemias, immunocytomas and marginal zone lymphomas (all in cluster I), individual lymphoma entities were distributed among at least 2 clusters. There was, however, a marked preponderance of mantle cel l lymphomas and diffuse follicular center lymphomas in duster I and of diff use large B-cell lymphomas and peripheral T-cell lymphomas in cluster 2. An aplastic large-cell lymphomas predominated in cluster 3 and responded best to therapy. (C) 1999 Wiley-Liss, Inc.