Proliferation in non-Hodgkin's lymphomas and its prognostic value related to staging parameters

In malignant lymphomas, cell kinetics has shown to be related with histologic type as well as with the clinical behaviour. The aim of our study was to investigate the relevance of cell proliferation parameters on overall survival in non-Hodgkin's lymphomas as well as their relationship with prognostic factors such as International Prognostic Index (IPI). We performed DNA-flow-cytometry (S-phase fraction and detection of DNA-aneuploidy) as well as cytologic examination and the AgNOR technique in material obtained by fine needle aspiration of lymph nodes at diagnosis. The majority of the patients were stage IV by Ann Arbor and intermediate risk by IPI (42/55). When analyzing all patients together, histologic type by the WHO classification, IPI and the presence of a DNA-aneuploid clone could not separate well patients with a different survival. For all patients, univariate Cox analysis revealed S-phase (SPF) and AgNOR parameters to be of prognostic value. In the multivariate analysis, however, only SPF remained in the final model. Yet, when stratifying for DNA-ploidy, only the total number of AgNORs/nucleus was an independent parameter. Looking only at the DNA-diploid cases, the AgNOR pattern remained the most important parameter, whereas for the DNA-aneuploid cases this was true for SPF. When studying patients with B large cell lymphoma separately, only DNA-ploidy was a prognostic factor. In summary, cell kinetic parameters reveal important prognostic information in NHL patients. Furthermore, DNA-aneuploidy seems to interfere with the analysis of the AgNOR pattern.