GROWTH-PATTERNS OF DIFFUSE NON-HODGKINS-LYMPHOMAS ESTIMATED FROM MITOTIC AND APOPTOTIC INDEXES

Growth rates of neoplasms could be calculated only on the basis of mit otic and apoptotic indices (MI and AI, respectively), assessed on tiss ue sections, if the duration of mitosis and apoptosis (T-m and T-a, re spectively) in vivo were known. For humans, this is practically never the case. What use then can be made of MI and AI to arrive at a relati ve, crude estimate of the state of growth? As a model system to study this problem, we chose diffusely growing stage I + II nonHodgkin's lym phomas (dNHL, n = 94), Cluster analysis revealed the existence of 3 hi ghly distinct groups of dNHL (clusters I, II and III) in the MI vs. AI per case plot, with a roughly linear relation between both parameters . Most nosologic entities defined by the REAL classification comprise cases that were represented in more than one cluster. We adopted the s imple formula CI (growth index) = XMI - AI, where X (= T-a/T-m) remain s to be evaluated. Based on the assumption that spontaneous regression s of dNHL are rare but do occur, we estimated that X = 2 or, possibly, 3 are best fits for the pooled dNHLs studied. With the assumption of X = 2, (i) 2MI - AI gave relatively lower values for dNHL than prolife rative indices such as %Ki-67(+) cells; (ii) values for 2MI/AI per clu ster showed a pattern inverse to that for %bcl-2+ cells; and (iii) a p lot of 2MI - AI vs. 2MI/AI per case allowed the recognition, especiall y among NHLs with a low cell turnover, of cases where accumulation of presumably longer-lived cells is an important factor in determining gr owth. (C) 1997 Wiley-Liss, Inc.