Cell cycle kinetics in malignant lymphoma studied with in vivo iododeoxyuridine administration, nuclear Ki-67 staining, and flow cytometry

ALIGNANT lymphomas constitute a heterogeneous M group of lymphoproliferative disorders with respect to presentation, clinical course, response to treatment, and prognosis. Histopathologic classification and clinical staging are considered suboptimal to predict the biologic and clinical behavior of these tumors. Therefore, additional parameters are urgently needed. The role of proliferative activity has received special attention. Different techniques have been used to study cell kinetics in lymphomas: measurement of the percentage of S-phase cells by DNA flow cytometry (FCM),'-'O assessment of the labeling index (LI) by in vitro incorporation of tritiated thymidine and autoradiography,"J2 and staining with the Ki-67 monoclonal antibody (MoAb), which reacts with a proliferation-associated nuclear antigen.13-17 The clinical impact of cell kinetics with respect to classification and prognosis of lymphomas remains questionable.ls This might be due to the limitations of the techniques available in a clinical setting. Measurement of the S-phase fraction is difficult to assess in aneuploid tumors.' Overestimation of the proliferative activity may occur due to arrested S-phase cells.19 Assessment of the thymidine LI requires ex vivo undisturbed growth of the tumor cells, and is timeconsuming. However, the major limitation of these techniques is that they provide only a partial and static kinetic From the Departments of Hematology, Pathology, and Dermatol