Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki67 labelling index, histological grade and prognosis

Abstract

The grading and prognostic assessment of oligodendrogliomas is severely constrained and there remains a need for improved diagnosis. Recently, we have identified the minichromosome maintenance (MCM) family of proteins as a novel class of proliferation markers. Mcm2 is a protein which forms part of the prereplicative complex. It is necessary for this complex to be assembled at origins of future DNA replication during the G1 phase to allow genome replication in the subsequent S phase. Our aim was to determine whether analysis of Mcm2 protein expression in oligodendrogliomas is of diagnostic value. Immunohistochemical staining for Mcm2 was performed on an archival series of 32 oligodendrogliomas. These tumours have been previously characterized for Ki67, mitotic labelling index and outcome. Cells showing expression of Mcm2 were quantified as a percentage to provide an Mcm2 labelling index. We have demonstrated a good correlation between Mcm2 and Ki67 labelling indices (r = 0.76, P < 0.01) but immunohistochemistry for Mcm2 consistently identified a higher proportion of cells. Mcm2 labelling index was higher in grade III than grade II tumours (P < 0.001). Cases with a high Mcm2 labelling index showed a poorer prognosis than those with a low index (P = 0.497) in univariate analysis, but with wide variation in this small series. Demonstration of Mcm2 expression is of value to demonstrate the proliferative fraction of tumours and is likely to be of prognostic value. Its study in a larger series is therefore warranted.