Polyadenylate polymerase enzymatic activity in mammary tumor cytosols: A new independent prognostic marker in primary breast cancer

Polyadenylate polymerase (PAP) is one of the enzymes involved in the format ion of the polyadenylate tail of the 3' end of mRNA, High levels of PAP act ivity were associated with rapidly proliferating cells, Here we evaluate th e prognostic value of PAP activity in breast cancer patients. PAP specific activity values were measured by a highly sensitive assay in the tumor cyto sols of 228 women with primary breast cancer. The median follow-up period w as 58 months. PAP specific activity values ranged from 2.1-39.4 units/mg pr otein in the breast tumor cytosols, and the activity was correlated with th e level of expression of the antigen. An optimal cutoff value of 5.5 units/ mg extracted protein was first defined by statistical analysis, PAP status was then compared with other established prognostic factors in terms of rel apse-free survival (RFS) and overall survival (OS), PAP activity levels had a tendency to increase with tumor-node-metastasis (TNM) stage and were hig her in node-positive patients. Evaluation of the prognostic value of PAP wa s performed using univariate and multivariate analyses. Univariate analysis showed that PAP-positive patients had a less favorable prognosis for both RFS (relative risk (RR) = 2.35; P < 0.001] and OS (RR = 3.15; P < 0.001). P AP significantly added to the prognostic power for RFS (RR = 2.51; P = 0.00 12) and OS (RR = 4.21; P < 0.001) in multivariate analysis, whereas patient age, tumor size, and nodal and ER status remained independent factors for predicting survival. When only node-negative patients were examined, PAP wa s found to be an independent factor for predicting RFS (RR = 3.68; P = 0.00 32) and OS (RR = 4.81; P < 0.001). PAP did not appear to have a prognostic significance for node-positive patients. PAP is a new prognostic factor for early recurrence and death in breast cancer patients. Our results suggest that PAP may be used as an independent unfavorable prognostic factor in nod e-negative breast cancer patients because there were no significant associa tions between PAP and the other prognostic indicators evaluated in this gro up of patients.