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. Int. J. Cancer 83:203–209, 1999. © 1999 Wiley-Liss, Inc.