Kim Sewha, Jung Woo Hee, Koo Ja Seung
Department of Pathology, Yonsei University College of Medicine Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
Tumour Biol. 2013 Oct;34(5):2683-9. doi: 10.1007/s13277-013-0819-7. Epub 2013 May 1.
The aim of this study was to investigate the expression of glutamine-metabolism-related proteins according to the histologic grade of phyllodes tumors (PTs) and to assess its clinical implication. We generated tissue microarrays of 224 PTs and performed immunohistochemical staining and western blot analysis of glutamine-metabolism-related molecules, including GLS1, GDH, and ASCT2. The associations between immunohistochemical results and clinicopathologic parameters were evaluated. The expression of GLS1 (p < 0.001), GDH (p < 0.001), and ASCT2 (p = 0.005) in stromal components significantly increased with worsening PT histological grade. GDH expression in epithelial components significantly increased in high-grade PT (p = 0.026). In western blot, stromal expression of GLS1, GDH, and ASCT2 increased as histologic grade increased. By univariate analysis, stromal GLS1 expression (p = 0.022) and stromal GDH expression (p = 0.009) were independent predictors of shorter DFS. Stromal GLS1 expression (p < 0.001) and stromal GDH expression (p < 0.001) were independent predictors of shorter OS. This study demonstrated that the stromal expression of the glutamine-metabolism-related proteins GLS1, GDH, ASCT2 increases with worsening histological PT grade.
本研究旨在根据叶状肿瘤（PTs）的组织学分级研究谷氨酰胺代谢相关蛋白的表达情况，并评估其临床意义。我们制作了224例PTs的组织芯片，并对包括GLS1、GDH和ASCT2在内的谷氨酰胺代谢相关分子进行了免疫组织化学染色和蛋白质印迹分析。评估了免疫组织化学结果与临床病理参数之间的相关性。随着PT组织学分级的恶化，基质成分中GLS1（p<0.001）、GDH（p<0.001）和ASCT2（p=0.005）的表达显著增加。高级别PT中上皮成分的GDH表达显著增加（p=0.026）。在蛋白质印迹中，随着组织学分级增加，GLS1、GDH和ASCT2的基质表达增加。单因素分析显示，基质GLS1表达（p=0.022）和基质GDH表达（p=0.009）是DFS缩短的独立预测因素。基质GLS1表达（p<0.001）和基质GDH表达（p<0.001）是OS缩短的独立预测因素。本研究表明，谷氨酰胺代谢相关蛋白GLS1、GDH、ASCT2的基质表达随着PT组织学分级的恶化而增加。
