Buta Marko, Džodić Radan, Đurišić Igor, Marković Ivan, Vujasinović Tijana, Markićević Milan, Nikolić-Vukosavljević Dragica
Surgical Oncology Clinic, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia.
School of Medicine, University of Belgrade, Dr Subotića 8, 11000, Belgrade, Serbia.
Tumour Biol. 2015 Sep;36(10):8193-200. doi: 10.1007/s13277-015-3573-1. Epub 2015 May 21.
We evaluated urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) prognostic value in postmenopausal, node-negative breast cancer patients bearing tumors with estrogen receptor (ER)/progesterone receptor (PR) expression, treated with locoregional therapy alone, within an early follow-up. We focused our analysis on tumors of histological grade II in order to improve its prognostic value and, consequently, to improve a decision-making process. The cytosol extracts of 73 tumor samples were used for assessing several biomarkers. ER and PR levels were measured by classical biochemical method. Cathepsin D was assayed by a radiometric immunoassay while both uPA and PAI-1 level determinations were performed by enzyme-linked immunosorbent assays. HER-2 gene amplification was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue. Patients bearing tumors smaller than or equal to 2 cm (pT1) or those with low PAI-1 levels (PAI-1 < 6.35 pg/mg) showed favorable outcome compared to patients bearing tumors greater than 2 cm (pT2,3) or those with high PAI-1 levels, respectively. Analyses of 4 phenotypes, defined by tumor size and PAI-1 status, revealed that patients bearing either pT1 tumors, irrespective of PAI-1 levels, or pT2,3 tumors with low PAI-1 levels, had similar disease-free interval probabilities and showed favorable outcome compared to those bearing pT2,3 tumors with high PAI-1 levels. Our findings suggest that tumor size and PAI-1, used in combination as phenotypes are not only prognostic but might also be predictive in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up period.
我们评估了尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂-1（PAI-1）在绝经后、淋巴结阴性且肿瘤表达雌激素受体（ER）/孕激素受体（PR）的乳腺癌患者中的预后价值，这些患者仅接受局部区域治疗，处于早期随访阶段。我们将分析重点放在组织学二级肿瘤上，以提高其预后价值，从而改进决策过程。73个肿瘤样本的细胞溶质提取物用于评估多种生物标志物。ER和PR水平通过经典生化方法测量。组织蛋白酶D通过放射免疫测定法检测，而uPA和PAI-1水平测定均通过酶联免疫吸附测定法进行。HER-2基因扩增通过原发性肿瘤组织中的显色原位杂交（CISH）确定。与肿瘤大于2 cm（pT2,3）的患者或PAI-1水平高的患者相比，肿瘤小于或等于2 cm（pT1）的患者或PAI-1水平低（PAI-1 < 6.35 pg/mg）的患者显示出良好的预后。对由肿瘤大小和PAI-1状态定义的4种表型的分析表明，无论PAI-1水平如何，患有pT1肿瘤的患者，或PAI-1水平低的pT2,3肿瘤患者，与PAI-1水平高的pT2,3肿瘤患者相比，具有相似的无病间期概率且预后良好。我们的研究结果表明，在早期随访期间，作为表型联合使用的肿瘤大小和PAI-1不仅具有预后价值，而且可能对淋巴结阴性、绝经后且患有组织学二级ER/PR表达肿瘤的乳腺癌患者具有预测价值。
