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.