Division of Hematology-Oncology, Department of Medicine, Seoul Paik Hospital, Inje University School of Medicine, Seoul, Korea.
Leuk Lymphoma. 2011 Feb;52(2):205-13. doi: 10.3109/10428194.2010.542261.
Hypoxia-associated proteins are commonly expressed as a consequence of disturbances in microcirculation. However, the clinical relevance of the proteins has never been studied in primary central nervous system lymphoma (PCNSL). The expression of hypoxia-inducible factor 1α (HIF-1α) and its downstream proteins, vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT-1), were evaluated in a central nervous system (CNS) lymphoma xenograft model and in human PCNSL tissue. In the CNS lymphoma xenograft model, the expression of HIF-1α, VEGF, and GLUT-1 co-localized in subsets of lymphoma cells adjacent to necrosis. In tumor specimens from 51 patients with PCNSL, positive HIF-1α staining was found in 26 patients (51.0%), positive VEGF in 30 (58.8%), and positive GLUT-1 in 17 (33.3%), and HIF-1α showed a significant correlation with VEGF (p < 0.05). However, no significant association was seen between hypoxia-associated protein positivity and unfavorable clinical characteristics. Thus, the results failed to show an association with shorter overall survival or time to progression, except that the percentage of lymphoma cells positive for GLUT-1 (>20%) was significantly associated with worse survival. In conclusion, hypoxia-associated proteins were expressed in PCNSL, suggesting a hypoxic microenvironment. However, the prognostic relevance of these proteins for PCNSL was not demonstrated in this study.
缺氧相关蛋白通常是由于微循环紊乱而表达的。然而，其在原发性中枢神经系统淋巴瘤（PCNSL）中的临床相关性从未被研究过。本研究在中枢神经系统淋巴瘤异种移植模型和人类 PCNSL 组织中评估了缺氧诱导因子 1α（HIF-1α）及其下游蛋白血管内皮生长因子（VEGF）和葡萄糖转运蛋白 1（GLUT-1）的表达。在中枢神经系统淋巴瘤异种移植模型中，HIF-1α、VEGF 和 GLUT-1 的表达在与坏死相邻的淋巴瘤细胞亚群中共同定位。在 51 例 PCNSL 患者的肿瘤标本中，26 例（51.0%）患者的 HIF-1α 染色阳性，30 例（58.8%）患者的 VEGF 阳性，17 例（33.3%）患者的 GLUT-1 阳性，且 HIF-1α 与 VEGF 呈显著相关性（p<0.05）。然而，缺氧相关蛋白阳性与不良临床特征之间无显著相关性。因此，结果未能显示与总生存时间或进展时间之间的相关性，除了 GLUT-1 阳性的淋巴瘤细胞百分比（>20%）与生存不良显著相关。总之，PCNSL 中表达了缺氧相关蛋白，表明存在缺氧微环境。然而，本研究并未证明这些蛋白对 PCNSL 的预后相关性。
