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目的观察缺氧诱导因子1α(HIF-1α)及其靶基因Glut-1蛋白在膀胱移行细胞癌和肾透明细胞癌中的表达及其临床意义。方法TransAMTM酶联法测定25例膀胱移行细胞癌,16例肾透明细胞癌组织及同一患者远离肿瘤5 cm的癌周正常对照组织中HIF-1α蛋白活性定量;用免疫组织化学方法,对58例膀胱移行细胞癌和38例肾透明细胞癌石蜡组织标本中Glut-1蛋白的表达进行检测。结果HIF-1含量在肾透明细胞癌组织中为(3．38±1．71)μg/孔板,明显高于癌旁正常肾组织(2．23±1．07)μg/孔板,差异有统计学意义(P=0．03)。HIF-1α在膀胱TCC与对照中含量低,差别小,膀胱癌组织HIF-1含量较癌旁正常膀胱组织相比,有增高趋势,但差异无统计学意义(P=0．60)。12例正常膀胱黏膜和16例正常肾组织中无Glut-1蛋白的表达,Glut-1蛋白在膀胱癌和肾癌组织表达均显著增强,Glut-1蛋白在膀胱移行细胞癌中广泛表达,阳性率为77．9％(45／58)。G1、G2、G3膀胱癌组织Glut-1阳性表达率分别为66．7％,89．1％和53．3％。Glut-1蛋白与膀胱肿瘤分级有差异(P=0．029);31例表浅性膀胱癌Glut-1阳性表达率为83．9％,浸润性膀胱癌Glut-1阳性表达率70．4％,两组比较差异无统计学意义(P=0．90),提示Glut-1蛋白的表达与肿瘤分期无关。本组58例均有2年以上的随访,其中31例表浅性膀胱癌2年内有19例复发,12例无复发,复发组19例与未复发组12例Glut-1蛋白的表达分布无差异(P=0．90),提示Glut-1蛋白的表达与表浅性膀胱癌复发无关。在肾透明细胞癌组织中存在Glut-1广泛表达86．9％(33／38)。但Glut-1蛋白的表达与肾癌分级,分期无关。结论HIF-1α的表达可能对肾癌发生,发展起着重要作用,但在膀胱癌中作用还需进一步研究;Glut-1基因参与了肾透明癌和膀胱移行细胞癌的形成过程。
Objective To investigate the expression and clinical significance of hypoxia inducible factor 1α (HIF-1α) and its target gene Glut-1 in bladder transitional cell carcinoma and renal clear cell carcinoma. Methods TransAMTM enzyme-linked immunosorbent assay was used to measure the activity of HIF-1α in 25 cases of transitional cell carcinoma of bladder, 16 cases of clear cell renal cell carcinoma and normal pericancerous tissue of 5 cm distant from tumor in the same patient. Immunohistochemistry was used to detect 58 cases Bladder transitional cell carcinoma and 38 cases of renal clear cell carcinoma paraffin tissue specimens of Glut-1 protein expression was detected. Results The level of HIF-1 in renal clear cell carcinoma tissues was (3.38 ± 1.71) μg / well, which was significantly higher than that in adjacent normal renal tissues (2.23 ± 1.07 μg / well) There was statistical significance (P = 0.03). The content of HIF-1α in bladder TCC was lower than that in control, but the difference was not significant. The expression of HIF-1 in bladder cancer was higher than that in adjacent normal tissues, but the difference was not statistically significant (P = 0.60). Glut-1 protein expression was significantly increased in bladder and renal cell carcinoma tissues, while Glut-1 protein was widely expressed in transitional cell carcinoma of urinary bladder, which was positive in 12 cases of normal bladder mucosa and 16 cases of normal renal tissues The rate was 77.9% (45/58). The positive rates of Glut-1 in G1, G2 and G3 were 66.7%, 89.1% and 53.3%, respectively. Glut-1 protein was significantly different from those of bladder tumor (P = 0.029). The positive rate of Glut-1 in 31 cases of superficial bladder cancer was 83.9% and the positive rate of Glut-1 in invasive bladder cancer was 70.4 %, No significant difference between the two groups (P = 0.90), suggesting that Glut-1 protein expression has nothing to do with the stage of the tumor. The group of 58 patients were followed up for more than 2 years, of which 31 cases of superficial bladder cancer within 2 years, 19 cases of recurrence, 12 cases without recurrence, recurrence group and non-recurrence group, 12 cases of Glut-1 protein expression and distribution (P = 0.90), suggesting that the expression of Glut-1 protein was not associated with the recurrence of superficial bladder cancer. Glut-1 is widely expressed in renal clear cell carcinoma tissues by 86.9% (33/38). However, the expression of Glut-1 protein has nothing to do with the grade and stage of renal cell carcinoma. Conclusions The expression of HIF-1α may play an important role in the occurrence and development of renal cell carcinoma. However, the role of HIF-1α in bladder cancer needs to be further studied. Glut-1 gene is involved in the formation of clear cell renal carcinoma and transitional cell carcinoma of bladder.