Kwon Ji Eun, Jung Woo-Hee, Koo Ja Seung
Department of Pathology, Ajou University School of Medicine, Suwon, Korea.
Tumour Biol. 2013 Feb;34(1):115-24. doi: 10.1007/s13277-012-0518-9. Epub 2012 Sep 18.
The purpose of this study was to investigate the association between the expression of hypoxia-inducible factor (HIF)-1α, insulin-like growth factor (IGF)-1, glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX), and monocarboxylate transporter (MCT)4, which are metabolism-related proteins in phyllodes tumors (PTs), and clinicopathologic factors and its implication. We used tissue microarrays to analyze 207 PTs and performed immunohistochemical staining against the glycolysis-related molecules HIF-1α, IGF-1, Glut-1, CAIX, and MCT4. We then compared the immunohistochemical results and clinicopathologic parameters. The expressions of HIF-1α, Glut-1, CAIX, and MCT4 in the stromal component of PTs increased (P = 0.019, P < 0.001, P = 0.045, and P < 0.001, respectively) with increasing tumor grade. According to univariate analysis, factors associated with shorter disease-free survival were Glut-1 expression (P = 0.001) and MCT4 expression (P < 0.001) in the stromal component, and the factors associated with shorter overall survival were IGF-1 expression (P = 0.012), Glut-1 expression (P < 0.001), CAIX expression (P = 0.039), and MCT4 expression (P < 0.001) in the stromal component. Our investigation of stromal expression of the metabolism-related proteins HIF-1α, IGF-1, Glut-1, CAIX, and MCT4 revealed that, as the PT grade increased, the stromal expression of HIF-1α, Glut-1, CAIX, and MCT4 significantly increased. This result suggested that increasing PT grade is associated with increased glycolysis in the stromal component.
本研究旨在探讨叶状肿瘤(PTs)中与代谢相关的蛋白质缺氧诱导因子(HIF)-1α、胰岛素样生长因子(IGF)-1、葡萄糖转运蛋白1(Glut-1)、碳酸酐酶IX(CAIX)和单羧酸转运蛋白(MCT)4的表达与临床病理因素之间的关联及其意义。我们使用组织芯片分析了207例PTs,并对糖酵解相关分子HIF-1α、IGF-1、Glut-1、CAIX和MCT4进行了免疫组织化学染色。然后,我们比较了免疫组织化学结果和临床病理参数。PTs间质成分中HIF-1α、Glut-1、CAIX和MCT4的表达随着肿瘤分级的增加而升高(分别为P = 0.019、P < 0.001、P = 0.045和P < 0.001)。单因素分析显示,间质成分中与无病生存期较短相关的因素是Glut-1表达(P = 0.001)和MCT4表达(P < 0.001),与总生存期较短相关的因素是间质成分中IGF-1表达(P = 0.012)、Glut-1表达(P < 0.001)、CAIX表达(P = 0.039)和MCT4表达(P < 0.001)。我们对代谢相关蛋白HIF-1α、IGF-1、Glut-1、CAIX和MCT4的间质表达进行研究发现,随着PT分级增加,HIF-1α、Glut-1、CAIX和MCT4的间质表达显著增加。这一结果表明,PT分级增加与间质成分中糖酵解增加有关。