MIB-1 and S-phase cell fraction predict survival in non-Hodgkin's lymphomas

Abstract

The monoclonal antibody anti-Ki67 is used to detect proliferating cells, but its main limitation is the requirement of fresh-frozen material.On a series of patients with non-Hodgkin's lymphoma, we used a Ki67 equivalent monoclonal antibody, the recently proposed MIB-1, on formalin-fixed histopathological material using microwave antigen retrieval.MIB-1 expression was analysed in relation to other proliferation indices, such as autoradiographic 3H-thymidine labelling index (3HTL1) and flow cytometric S-phase cell fraction (FCM-S) and to pathological status.Moreover, the prognostic relevance of the cell kinetic indices was defined in uni-and multivariate analyses including histology and tumour stage.The relationship between MIB-1 index and the other proliferation indices was statistically significant even though the correlation coefficient was around 0.6.The MIB-1 index was also related to the REAL (Revised European American Lymphoma) classification, but not to the Ann Arbor stage classification.Univariate analysis showed that the MIB-1 index was a significant predictor of 6-year survival in the overall series and in distinctly analysed low-grade and high-grade lymphoma subgroups.With regard to S-phase indices, 3HTLI was a powerful prognosticator in patients with high-grade histologies and FCM-S in patients with low-grade histologies.Multivariate analyses revealed that MIB-1 indiex, 3HTLI and FCM-S retained their prognostic significance independent of histology.In conclusion, the MIB-1 antibody provides prognostic information in non-Hodgkin's lymphomas and has the main advantage that it can be used in formalin-fixed, paraffin-embedded specimens.The prognostic definition and the choice of therapy in non-Hodgkin's lymphomas (NHL) are based on clinical staging and on histological classifications, which distinguish NHL with an indolent behaviour from those with an aggressive one.However, within the two subgroups there are entities with considerably different biological and clinical outcomes (Urba et al. 1990, Armitage 1993, Hiddemann & Unterhalt 1994).During the last 20 years, accumulating information has shown that cell proliferation activity may contribute to a more precise identification of patients at different risk.Some studies have addressed quantification of the S-phase cell fraction by utilizing active incorporation of 'H-thymidine, iodo-or bromodeoxyuridine (Kawauchi et al.