Department of Nuclear Medicine and Radiation Protection, University Hospital Center Zagreb, Zagreb, Croatia.
Otolaryngol Head Neck Surg. 2013 Oct;149(4):533-40. doi: 10.1177/0194599813496374. Epub 2013 Jul 8.
To investigate the prognostic value of urokinase-type plasminogen activator (uPA) and its inhibitor, type-1 plasminogen activator inhibitor (PAI-1), in differentiated thyroid cancer.
Prospective cohort study.
University hospital.
Cytosolic concentrations of uPA and PAI-1 were determined in 105 patients with differentiated thyroid carcinoma and normal matched tissues using an enzyme-linked immunoassay (ELISA).
Both uPA and PAI-1 concentrations were significantly higher in differentiated thyroid tumors (uPA = 0.509 ± 0.767 and PAI-1 = 6.337 ± 6.415 ng/mg) compared to normal tissues (uPA = 0.237 ± 0.051, P < .001; PAI-1 = 2.368 ± 0.418 ng/mg, P < .001). uPA and PAI-1 were significantly higher if extrathyroidal invasion (uPA, P = .015; PAI-1, P < .001) or distant metastasis (PAI-1 P < .001) was present, as well as in tumors whose size exceeded 1 cm in diameter (uPA, P = .002; PAI-1, P = .001). Survival analysis revealed the significant impact of both uPA and PAI-1 on progression-free survival (PFS) (82.22 vs 49.478 months for patients with low and high uPA, respectively, P < .001; 87.068 vs 44.964 months for patients with low and high PAI-1, respectively, P < .001). Univariate analysis showed that gender, tumor size, tumor grade, extrathyroid invasion, local lymph node involvement, distant metastasis, uPA, and PAI-1 were significant predictors of PFS. However, multivariate analysis identified only distant metastasis and tumor tissue uPA and PAI-1 as independent prognostic factors.
These findings indicate that high uPA and PAI-1 levels represent independent unfavorable prognostic factors in patients with differentiated thyroid carcinoma.
探讨尿激酶型纤溶酶原激活物(uPA)及其抑制剂 1 型纤溶酶原激活物抑制剂(PAI-1)在分化型甲状腺癌中的预后价值。
前瞻性队列研究。
大学医院。
采用酶联免疫吸附试验(ELISA)检测 105 例分化型甲状腺癌患者及正常配对组织中 uPA 和 PAI-1 的细胞浆浓度。
与正常组织相比(uPA=0.237±0.051，P<.001；PAI-1=2.368±0.418 ng/mg)，分化型甲状腺肿瘤(uPA=0.509±0.767，PAI-1=6.337±6.415 ng/mg)中 uPA 和 PAI-1 的浓度均显著升高。如果存在甲状腺外侵犯(uPA，P=0.015；PAI-1，P<.001)或远处转移(PAI-1，P<.001)，或者肿瘤直径超过 1cm(uPA，P=0.002；PAI-1，P=0.001)，uPA 和 PAI-1 均显著升高。生存分析显示，uPA 和 PAI-1 对无进展生存率(PFS)均有显著影响(uPA 低和高组患者的 PFS 分别为 82.22 个月和 49.478 个月，P<.001；PAI-1 低和高组患者的 PFS 分别为 87.068 个月和 44.964 个月，P<.001)。单因素分析显示，性别、肿瘤大小、肿瘤分级、甲状腺外侵犯、局部淋巴结受累、远处转移、uPA 和 PAI-1 是 PFS 的显著预测因子。然而，多因素分析仅识别出远处转移和肿瘤组织 uPA 和 PAI-1 是独立的预后因素。
这些发现表明，uPA 和 PAI-1 水平升高是分化型甲状腺癌患者的独立不良预后因素。
