mcm2 geminin and ki67 define proliferative state and are prognostic markers in renal cell carcinoma purpose the origin licensing factors minichromosome maintenance 2 mcm2 and geminin have recently been identified as critical regulators of growth and differentiation here we have investigated the regulation of these licensing factors together with ki67 to further elucidate the cell cycle kinetics of renal cell carcinoma rcc furthermore we have examined the role of ki67 mcm2 and geminin in diseasefree survival after nephrectomy in patients with localized rccexperimental design tissue sections from 176 radical nephrectomy specimens were immunohistochemically stained with mcm2 geminin and ki67 antibodies labeling indices li for these markers were compared with clinicopathologic parameters median followup 44 monthsresults in rcc mcm2 is expressed at much higher levels than ki67 and geminin respectively medians 416 73 and 35 p 12 and age were found to be independent prognostic markersconclusions although ki67 is identified as an independent prognostic marker semiquantitative assessment is difficult due to the very low proliferative fraction identified by this marker in contrast mcm2 identifies an increased growth fraction that is closely linked to grade provides prognostic information and is amenable to semiquantitative analysis in routine pathologic assessment