Minisini Alessandro Marco, Fabbro Dora, Di Loreto Carla, Pestrin Marta, Russo Stefania, Cardellino Giovanni Gerardo, Andreetta Claudia, Damante Giuseppe, Puglisi Fabio
Department of Medical Oncology, University of Udine, Udine, Italy.
Am J Clin Pathol. 2007 Jul;128(1):112-7. doi: 10.1309/M0GXVXA89BVLJ5C9.
The urokinase plasminogen activator (uPA) system includes uPA and plasminogen activator inhibitor types 1 (PAI-1) and 2 that mainly act by regulating extracellular matrix degradation, and it is involved in tumor progression. The -675 4G/5G polymorphism of the PAI-1 gene regulates PAI-1 activity in serum. We aimed at studying the -675 4G/5G polymorphism of the PAI-1 gene and uPA, PAI-1, and cyclooxygenase-2 (COX-2) immunohistochemical expression in a series of breast cancer cases. Homozygosity for the 4G allele of the PAI-1 gene was associated with node-positive breast cancer ( P = .02). We showed a direct correlation between uPA and estrogen receptor expression ( P = .03); negative uPA expression was associated with negative hormonal expression, high tumor grade, and high proliferation index ( P < .05). A direct correlation was seen between uPA and PAI-1, uPA and COX-2, and PAI-1 and COX-2 expression ( P < .05). Interaction between uPA and COX-2 systems in breast cancer deserves further study.
尿激酶型纤溶酶原激活物（uPA）系统包括uPA以及1型和2型纤溶酶原激活物抑制剂（PAI-1），它们主要通过调节细胞外基质降解发挥作用，并且参与肿瘤进展。PAI-1基因的-675 4G/5G多态性可调节血清中PAI-1的活性。我们旨在研究一系列乳腺癌病例中PAI-1基因的-675 4G/5G多态性以及uPA、PAI-1和环氧合酶-2（COX-2）的免疫组化表达。PAI-1基因4G等位基因的纯合性与淋巴结阳性乳腺癌相关（P = 0.02）。我们发现uPA与雌激素受体表达之间存在直接相关性（P = 0.03）；uPA阴性表达与激素表达阴性、肿瘤分级高和增殖指数高相关（P < 0.05）。uPA与PAI-1、uPA与COX-2以及PAI-1与COX-2表达之间均存在直接相关性（P < 0.05）。乳腺癌中uPA与COX-2系统之间的相互作用值得进一步研究。
