Proliferation Kinetics of Non-Hodgkin's Lymphoma: Correlation With Histologic Grade According to the International Working Formulation

The growth fractions of 35 non-Hodgkin's lymphomas (NHL), classified according to the International Working Formulation (IWF) as low, intermediate, or high grade, and 7 lymphoid hyperplasias were analyzed. The assays used were: (1) Ki67 antigen expression using a monoclonal anti-Ki67 antibody and indirect immunofluorescence microscopy on cytocentrifuge slide preparations (%Ki67); (2) flow cytometric assay of incorporated bromodeoxyrudine (BrDU) during short-term cell culture with a fluo rescein-labeled anti-BrDU antibody (%BrDU); and (3) flow cytometric cell cycle analy sis following propidium iodide incorporation (%S-PI). When the results obtained by these three methods were analyzed according to IWF histologic/prognostic groups, a consistent trend was seen: the values obtained increased with increasing tumor grade, and all three methods could discriminate low- from high-grade NHL. Additionally, %Ki67 and %BrDU discriminated between intermediate- and high-grade NHL. None of the methods discriminated between NHL of low and intermediate grades or between such lymphomas and lymphoid hyperplasia. Multivariate discriminant analysis using a panel consisting of the variables %Ki67, %BrDU, and %S-PI could distinguish between high-grade NHL and all other NHL, as well as between high-grade and intermediate- grade NHL, greater than 90% of the time. In the analyses that resulted in significant discriminant functions, %Ki67 had the best statistically determined discriminatory ability of the three methods. The correlation between cell cycle kinetics and IWF grade suggests that such measurements may have prognostic significance. Int J Surg Pathol 1(1): 33-42, 1993.