肾透明细胞癌中血管抑制蛋白-1与微血管密度的检测及临床意义

Detection and clinical significance of Vasohibin-1 and microvessel density in clear cell renal cell carcinoma

目的:探讨肾透明细胞癌内血管抑制蛋白-1(Vasohibin-1,VASH1)以及微血管密度(microvessel density,MVD)检测与肾透明细胞癌患者预后之间的关系。方法:采用免疫组织化学方法半定量测定肾透明细胞癌标本VASH1染色的平均细胞累积光密度(average optical density,AOD),并测定CD34标记的MVD。用Cox回归模型分析患者的临床和病理因素与生存预后之间的关系。结果:肾癌组织中VASH1的AOD为0.0435±0.0178,MVD均值为55±34,两者的表达均与病理分期和肿瘤内的凝固性坏死有显著相关性(P<0.05)。相关性分析显示VASH1与MVD的表达呈负相关(r=-0.641,P<0.01)。单因素回归分析证明高VASH1组肾透明细胞癌预后显著差于低VASH1组,差异均有统计学意义(HR=2.96,P<0.05)。多因素回归分析显示患者年龄、病理分期以及肿瘤内凝固性坏死与患者的总体生存(HR=4.90,P<0.05;HR=3.08,P<0.05;HR=3.05,P<0.05)和无复发生存(HR=3.91,P<0.05;HR=2.85,P<0.05;HR=3.24,P<0.05)呈显著相关性。结论:在肾透明细胞癌中,低VASH1表达提示较好的预后,而患者年龄、病理分期以及肿瘤内凝固坏死是肾透明细胞癌的独立预后因素。此研究仍待前瞻性大规模临床试验的验证。

Objective：To investigate the expression of Vasohibin-1（VASH1）and microvessel density（MVD）marked with CD34 in clear cell renal cell carcinoma（ccRCC）and analyze their correlations with prognosis.Method：Expressions of VASH1 and CD34in their tissue samples were detected by immunohistochemical（IHC）staining.For VASH1 assessment,the staining intensity of positive tumor cells were evaluated semi-quantitatively and measured by average optical density（AOD）for further analysis.MVD was counted using Weidner＇s method.Statistical analysis was performed using SPSS 19.0.Result：The AOD of VASH1 in the 79 cancer tissues was 0.0435±0.0178.The MVD value marked by CD34 in the 79 cancer tissues was（55±34）profiles/HPF.The expression of MVD and VASH1 significantly varied with tumor stages and necrosis presence（P〈0.05）.Assessed by Spearman＇s correlation,the expression of VASH1 was negatively associated with MVD（r=-0.641,P〈0.01）.The overall survival（OS）and recurrence-free survival（RFS）in ccRCC patients with high VASH1 expression were significantly worse than those low VASH1expression（P〈0.05）.The multivariate analysis showed that age,tumor stage and necrosis presence were significantly correlated with OS and RFS in ccRCC patients.Conclusion：Lower expression of VASH1 indicates better prognosis of ccRCC.Patients＇ age,tumor stage and necrosis presence were independent prognostic factors for ccRCC.However,more large-scale,prospective trials are needed to confirm our findings.