Polyadenylate polymerase enzymatic activity in mammary tumor cytosols: A new independent prognostic marker in primary breast cancer.Cancer Res. 2000 Oct 01; 60(19):5427-33.CR
Polyadenylate polymerase (PAP) is one of the enzymes involved in the formation of the polyadenylate tail of the 3' end of mRNA. High levels of PAP activity were associated with rapidly proliferating cells. Here we evaluate the prognostic value of PAP activity in breast cancer patients. PAP specific activity values were measured by a highly sensitive assay in the tumor cytosols of 228 women with primary breast cancer. The median follow-up period was 58 months. PAP specific activity values ranged from 2.1-39.4 units/mg protein in the breast tumor cytosols, and the activity was correlated with the 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 relapse-free survival (RFS) and overall survival (OS). PAP activity levels had a tendency to increase with tumor-node-metastasis (TNM) stage and were higher in node-positive patients. Evaluation of the prognostic value of PAP was 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). PAP significantly added to the prognostic power for RFS (RR = 2.51; P = 0.0012) 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 was found to be an independent factor for predicting RFS (RR = 3.68; P = 0.0032) 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 node-negative breast cancer patients because there were no significant associations between PAP and the other prognostic indicators evaluated in this group of patients.