Expression of VHL, VEGF and HIF-1α in endolymphatic sac tumors

Abstract

Objective: To investigate the expression of von Hippel-Lindau (VHL), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α) in endolymphatic sac tumor (ELST) and its clinical significance, and to analyze its association with VHL gene mutation. Methods: Twenty-four cases of ELST, which were surgically resected and diagnosed by pathological examination in Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China during 2012-2020, were recruited as the ELST group, and 24 cases of otitis media diagnosed in the same hospital were selected as the control group. The expression of VHL, VEGF, and HIF-1α was assessed using EnVision immunohistochemical staining and compared between the ELST and control groups. Sanger sequencing was performed to detect the VHL mutation status in 24 ELSTs. The correlations among VHL, VEGF and HIF-1α expression were analyzed. The associations of VHL, VEGF and HIF-1α expression with age of onset, gender, tumor size, bone invasion and clinical stage in ELST were also analyzed. Results: The expression rate of VHL in the ELST group was significantly lower than that in the control group (P<0.05), but the expression rates of VEGF and HIF-1α in the ELST group were significantly higher than those in the control group (P<0.05). VHL expression was inversely correlated with VEGF and HIF-1α expression. The expression of VEGF and HIF-1α was associated with bone invasion and clinical stage (P<0.05), but the expression of VHL, VEGF and HIF-1α had no significant associations with the age of onset, gender, or tumor size of ELST (P>0.05). Conclusions: The expression of VHL is decreased while that of VEGF and HIF-1α increased in ELST. Expression of VHL is inversely correlated with that of VEGF and HIF-1α. The expression of VEGF and HIF-1α is correlated with bone invasion and clinical stage. Thus, VEGF and HIF-1α may be therapeutic targets of ELST.目的： 探讨希佩尔-林道（VHL）、血管内皮生长因子（VEGF）、缺氧诱导因子1α（HIF-1α）在内淋巴囊肿瘤（ELST）中的表达及临床意义，分析其与VHL基因突变的相关性。 方法： 收集2012—2020年于首都医科大学附属北京同仁医院手术切除并经病理检查明确诊断为ELST的病例24例为实验组，选取24例临床及病理诊断为中耳炎的病例为对照组。免疫组织化学染色EnVision二步法检测VHL、VEGF、HIF-1α在ELST及对照组中的表达情况，Sanger测序检测24例ELST中VHL基因突变情况。比较VHL、VEGF、HIF-1α在两组中表达情况，统计分析VHL、VEGF、HIF-1α表达的相关性及在ELST中与发病年龄、肿瘤大小、骨质侵袭、临床分期等的相关性。 结果： VHL在ELST中阳性表达率显著低于对照组（P<0.05），VEGF、HIF-1α在ELST中阳性表达率显著高于对照组（P<0.05），VHL与VEGF、HIF-1α的表达呈负相关；VHL、VEGF、HIF-1α的表达与ELST发病年龄、性别、肿瘤大小的差异无统计学意义（P>0.05），VEGF、HIF-1α的表达与骨质侵袭、临床分期的差异有统计学意义（P<0.05）。 结论： ELST中VHL表达降低、VEGF、HIF-1α表达升高；VHL与VEGF、HIF-1α的表达呈负相关；VEGF、HIF-1α的阳性表达与骨质侵袭、临床分期呈正相关。VEGF、HIF-1α可能成为ELST的靶向治疗靶点。.