Improvement of breast cancer prognostication using cell kinetic-based silver-stainable nucleolar organizer region quantification of the MIB-1 positive tumor cell compartment

Recently, it was stated that the proliferative activity (P) of a cell popul ation could be indirectly calculated by multiplying the MIB-1 immunopositiv ity and silver-stainable nucleolar organizer region (AgNOR) features extrac ted exclusively in MIB-1 positive (pos.) nuclei: P=MIB- 1xAgNOR(MIB-1pos). To study the prognostic significance of this hypothesis, MIB-1 immunohistoc hemistry and AgNOR staining were applied on a series of 89 cases of breast cancer with an 8-year follow-up period. The mean MIB-1 immunopositivity (MI B-1(mean)) was evaluated immunohistometrically on paraffin sections using a TV image analysis system CM-2 (Hund, Wetzlar, Germany). Later, a combined MIB-1/AgNOR staining was applied and evaluated using a TV image analysis sy stem AMBA (IBSB, Berlin, Germany). The AgNOR features of 150 randomly chose n tumor nuclei were investigated, irrespective of their MIB-1 status (AgNOR count, AgNOR area). Later, a second measurement was performed on 100 MIB-1 positive tumor nuclei exclusively (AgNOR count(MIB)-(1pos.5) AgNOR area(MI B-1pos.)). AgNOR count and AgNOR count(MIB-1pos.), showed a different data distribution [2.7 +/-0.7 (mean +/- SD) vs 3.9 +/-1.1; r=0.315, P=0.014]. Si milar results were obtained for AgNOR area and AgNOR area(MIB-1pos.) (5.1 /-2.1 mum(2) vs 7.5 +/-2.4 mum(2); r-0.501, P<0.001). Kaplan-Meier survival curves revealed significant differences for MLB-1(mean), (P=0.0018) and Ag NOR area(MIB-1pos) (P=0.0340). In Cox models, both parameters provided Inde pendent prognostic information. Using their combination, the P, three group s of patients with statistically different survival could be separated (P=0 .0014). Thus, the combination of MIB-1-immunopositivity and AgNOR measureme nts in MIB-1 positive nuclei appears to be more useful in breast cancer pro gnosis than the exclusive application of one of the two methods. By this co mbined application, probably effects of tumor biology are represented more precisely.