Jevrić, Marko (43761174500)Marko (43761174500)JevrićMatić, Ivana Z. (36572349500)Ivana Z. (36572349500)MatićKrivokuća, Ana (36466506600)Ana (36466506600)KrivokućaCrnogorac, Marija Dordic (57193949676)Marija Dordic (57193949676)CrnogoracBesu, Irina (34567735200)Irina (34567735200)BesuDamjanović, Ana (7004519598)Ana (7004519598)DamjanovićBranković-Magić, Mirjana (55886308600)Mirjana (55886308600)Branković-MagićMilovanović, Zorka (25228841900)Zorka (25228841900)MilovanovićGavrilović, Dušica (8849698200)Dušica (8849698200)GavrilovićSusnjar, Snezana (6603541648)Snezana (6603541648)SusnjarKisić Tepavčević, Darija (57218390033)Darija (57218390033)Kisić TepavčevićStanojković, Tatjana (7801658230)Tatjana (7801658230)Stanojković2025-07-022025-07-022019https://doi.org/10.1186/s12885-018-5255-zhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059978383&doi=10.1186%2fs12885-018-5255-z&partnerID=40&md5=6840b31339528754218e470b2e3b5a61https://remedy.med.bg.ac.rs/handle/123456789/12852Background: The aim of this study was to evaluate the prognostic potential of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) tumor tissue levels and examine the association between these biomarkers and classical prognostic factors in early node-negative luminal breast cancer patients. The clinical value of 4G/5G variants of PAI-1 gene was evaluated. Patients and methods: This study involved 81 node-negative, estrogen receptor-positive and/or progesterone receptor-positive and human epidermal growth factor receptor 2-negative operable breast cancer patients who underwent radical surgical resection and received adjuvant endocrine therapy. Determination of uPA and PAI-1 concentrations in the breast cancer tissue extracts was performed using FEMTELLE® uPA/PAI-1 ELISA. An insertion (5G)/deletion (4G) polymorphism at position - 675 of the PAI-1 gene was detected by PCR-RFLP analysis. Results: Our research showed that patients with uPA tumor tissue levels higher than 3 ng/mg of protein had significantly reduced disease-free survival (DFS) and overall survival (OS) when compared to patients with uPA tumor tissue levels lower or equal to 3 ng/mg of protein. Patients with PAI-1 tumor tissue levels higher than 14 ng/mg of protein had significantly decreased OS in comparison with patients with PAI-1 tumor tissue levels lower or equal to 14 ng/mg of protein. ROC analysis confirmed the uPA and PAI-1 discriminative potential for the presence/absence of relevant events in these patients and resulted in higher cut-off values (5.65 ng/mg of protein for uPA and 27.10 ng/mg of protein for PAI-1) than standard reference cut-off values for both biomarkers. The prognostic importance of uPA and PAI-1 ROC cut-off values was confirmed by the impact of uPA higher than 5.65 ng/mg of protein and PAI-1 higher than 27.10 ng/mg of protein on poorer DFS, OS and event-free survival (EFS). We observed that patients with dominant allele in PAI-1 genotype (heterozygote and dominant homozygote, - 675 4G/5G and - 675 5G/5G) had significantly increased DFS, OS and EFS when compared with patients with recessive homozygote genotype (- 675 4G/4G). Conclusion: Our study indicates that uPA and PAI-1 tumor tissue levels and 4G/5G variants of PAI-1 gene might be of prognostic significance in early node-negative luminal HER2-negative breast cancer patients treated with adjuvant endocrine therapy. © 2019 The Author(s).Adjuvant endocrine therapyLuminal/HER2-negative, node-negative breast cancerPAI-1PAI-1 -675 4G/5G polymorphismPrognosticuPA