Replication protein A: a reliable biologic marker of prognostic and therapeutic value in human astrocytic tumors

SummaryReplication protein A is a single-stranded DNA–binding protein that is required for the stabilization of single-stranded DNA and identified in replication foci where members of cyclin-dependent kinases–cyclin complexes are also present. In this study, we investigated the expression of replication protein A1 and replication protein A2 subunits of replication protein A protein in correlation with cyclins D2 and D3 and nuclear factor κB expression and assessed their prognostic significance in 66 patients with astrocytomas. Statistically significant positive associations emerged between (a) replication protein A1 and replication protein A2 protein expression (P < .0001); (b) cyclins D2 and D3 expression (P < .0001); (c) replication protein A1, replication protein A2, and cyclins D2 and D3 expression and histologic grade (P = .0001 in all correlations); (d) replication protein A1 and cyclin D2 or D3 expression (P < .0001 in both relationships); and (e) replication protein A2 and cyclin D2 or D3 expression (P < .0001 in both relationships). Nuclear factor κB1/p50 expression was positively correlated with replication protein A1, replication protein A2, and cyclins D2 and D3 expression, although these relationships failed to retain statistical significance when they were adjusted for histologic grade. Replication protein A2 expression seemed to independently affect survival in grade IV (P = .005) as well as in the entire cohort (P = .006). None of the molecules under study seemed to influence survival in lower grades (II/III), either by univariate or by multivariate analysis. In conclusion, replication protein A1, replication protein A2, and cyclins D2 and D3 seem to have a parallel role in the promotion of cell cycle in astrocytic tumors being implicated in the malignant progression of these neoplasms. Moreover, replication protein A2 protein seems to be a useful prognostic indicator in patients with astrocytomas.