HIF 1 与CA 在肾细胞癌中的表达及临床意义

　　【摘要】 目的 探讨缺氧诱导因子-1α(HIF-1α)与碳酸酐酶9(CAⅨ)在肾细胞癌中的表达及相互关系。方法 采用免疫组织化学P-V方法检测54例肾癌石蜡标本切片中HIF-1α和CAⅨ的表达，并探讨其与临床病理因素之间的关系。结果 HIF-1α在肾癌组织中表达阳性率为55.6%(30/54)，其表达与不同临床分期、病理分级有关(P<0.05) ,与组织学类型无关(P>0.05);CAⅨ在肾癌组织中表达阳性率为68.5%(37/54)，其表达与不同临床分期、病理分级及组织学类型无关(P>0.05);HIF-1α和CAⅨ在肾癌组织中的表达呈正相关(r=0.437，P=0.001)。结论 肾癌中HIF-1α和CAⅨ的高表达和高相关性提示了以缺氧诱导因子通路为基础的分子靶向治疗的可行性。

　　【关键词】 肾细胞癌;缺氧诱导因子-1α;碳酸酐酶9

　　The overexpression and clinical significance of hypoxia-inducible factor-1 alpha and carbonic anhydrase Ⅸ in renal cell carcinoma

　　PENG Qiyu, WEN Rumin, XUE Song

　　Department of Urology， Affiliated Hospital of Xuzhou Medical College, Xuzhou， Jiangsu 221002， China

　　Abstract: Objective To investigate the expression of HIF-1α and CAⅨ in renal cell carcinoma (RCC) and to evaluate their significance. Methods The expressions of HIF-1α and CAⅨ were tested by immunohistochemistry in 54 specimens of RCC tissue, with the results analyzed by relating them to the clinical stage and pathological grade. Results The HIF-1α expression in RCC tissue was 55.6%, not related to the histological type (P>0.05), but related to the clinical stage and pathological grade of RCC (P<0.05) . The CAⅨ expression in RCC tissue was 68.5% positive, not related to the histological type, pathological grade or clinical stage of RCC (P>0.05). The expression of HIF-1α was positively correlated with the expression of CAⅨ (r=0.437, P=0.001). Conclusion The overexpression and high correlation of HIF-1α and CAⅨ in renal cell carcinoma support the feasibility of using targeted molecular therapy to treat RCC.

　　Key words: renal cell carcinoma (RCC); hypoxia-inducible factor-1 alpha; carbonic anhydrase Ⅸ

　　肾细胞癌(RCC)在成人泌尿生殖系统肿瘤中发病率仅次于膀胱癌居第二位，且对放化疗、生物治疗不敏感，预后较差。肾癌的发生机制复杂，约60%的肾癌患者存在抑癌基因——希佩尔-林道基因(VHL)的突变[1]，当VHL突变或失活后，VHL蛋白缺乏，在氧含量正常的情况下，也无法降解缺氧诱导因子-1α(HIF-1α)，使HIF-1α聚集导致下游靶基因血管内皮生长因子(VEGF)、碳酸酐酶9(CAⅨ)、葡萄糖转运蛋白1(GLUT-1)、促红细胞生成素(EPO)等基因表达，激活多激酶信号通路，导致肿瘤细胞增殖

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