Scorilas A, Talieri M, Ardavanis A, Courtis N, Dimitriadis E, Yotis J, Tsiapalis C M, Trangas T
G. Papanikolaou Research Center of Oncology, Athens, Greece.
Cancer Res. 2000 Oct 1;60(19):5427-33.
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.
聚腺苷酸聚合酶（PAP）是参与信使核糖核酸（mRNA）3'端聚腺苷酸尾形成的酶之一。高水平的PAP活性与快速增殖的细胞相关。在此，我们评估PAP活性在乳腺癌患者中的预后价值。通过高灵敏度检测法测定了228例原发性乳腺癌女性患者肿瘤胞质溶胶中的PAP比活性值。中位随访期为58个月。乳腺癌肿瘤胞质溶胶中的PAP比活性值在2.1 - 39.4单位/毫克蛋白质之间，且该活性与抗原表达水平相关。通过统计分析首次确定了提取蛋白的最佳临界值为5.5单位/毫克。然后就无复发生存期（RFS）和总生存期（OS）而言，将PAP状态与其他既定的预后因素进行比较。PAP活性水平有随肿瘤-淋巴结-转移（TNM）分期增加的趋势，且在淋巴结阳性患者中更高。使用单因素和多因素分析评估PAP的预后价值。单因素分析显示，PAP阳性患者在RFS（相对风险（RR）= 2.35；P < 0.001）和OS（RR = 3.15；P < 0.001）方面的预后均较差。在多因素分析中，PAP显著增强了对RFS（RR = 2.51；P = 0.0012）和OS（RR = 4.21；P < 0.001）的预后预测能力，而患者年龄、肿瘤大小以及淋巴结和雌激素受体状态仍是预测生存的独立因素。当仅检查淋巴结阴性患者时，发现PAP是预测RFS（RR = 3.68；P = 0.0032）和OS（RR = 4.81；P < 0.001）的独立因素。PAP对淋巴结阳性患者似乎没有预后意义。PAP是乳腺癌患者早期复发和死亡的一个新的预后因素。我们的结果表明，PAP可作为淋巴结阴性乳腺癌患者独立的不良预后因素，因为在该组患者中PAP与其他评估的预后指标之间无显著关联。
