应用荧光原位杂交技术检测膀胱癌的研究

Study on the detection of bladder cancer by fluorescence in situ hybridization

目的应用荧光原位杂交((fluorescence in situ hybridization,FISH)技术检测膀胱癌患者尿液脱落细胞中染色体异常,评估FISH在中国人群中诊断膀胱癌的作用。方法2007年1月至2008年8月,随机留取20例良性前列腺增生症患者的新鲜尿液,用3号和7号、17号及p16位两组混合探针,通过在尿液脱落细胞标本上进行FISH检测,建立正常人群的阈值;其后随机留取30例门诊膀胱镜活检证实的膀胱癌患者的尿液,同时进行尿液脱落细胞的细胞形态学分析及FISH检测,对比检查结果。结果3号、7号和17号染色体非整倍性改变及p16位点异常正常阈值分别为8.5%、7.1%、6.8%和9.2%,FISH与细胞学检查总敏感性分别为76.6%和43.3%(P<0.05)。T_(is)及T_a、T_1患者FISH检测的敏感性分别为80.0%和64.2%,脱落细胞组织学检测显示敏感性分别为40.0%和35.7%;T_(2-3)患者FISH的敏感性为90.9%,而脱落细胞组织学检测为54.7%(P<0.05),低级别尿路上皮癌FISH及细胞学敏感性分别为68.4%和31.6%;高级别分别为90.9%和63.6%。结论与尿液脱落细胞组织学检测相比,对尿液脱落细胞进行FISH检测可以提高膀胱癌的诊断率,FISH可以作为诊断膀胱癌的一种无创伤的新方法。

Objective To use fluorescence in situ hybridization （FISH） for detecting abnormal chromosomes of exfoliated urothelial cells in urine voided by urinary bladder cancer patients in order to evaluate the usefulness of FISH in the diagnosis of transitional cell carcinoma （TCC） of the bladder. Methods From 2007 to 2008, the fresh urine voided by twenty patients with benign prostatic hyperplasia served as control group. The FISH probes were targeted to chromosomes 3 and 7,17and p16. FISH was performed on exfoliated urothelial cells in urine to get the threshold value of healthy adult. Urine voided by thirty patients with confirmed bladder TCC by cystoscopy and biopsy was collected and examined by cytologic analysis and FISH. Results The threshold of chromosomes 3 and 7,17and p16 were 8.5% ,7. 1% ,6. 8% ,9. 2% respectively. FISH test had an overall sensitivity of 76. 6%, significantly greater than that of cytology, the sensitivity of which was 43.3 % （P = 0. 008 ）. The sensitivity of FISH in patients with Tis and Ta, T1 was 80. 0% and 64. 2% ,and that of cytology was 40. 0% and 35.7%. The sensitivity of FISH and cytology in T2-3 patients was 90. 9% and 54.7% respectively. The sensitivity of the two methods for the low-grade tumors was 68.4% and 31.6% ,and for high-grade tumors was 90. 9% and 63.6%, respectively. Conclusions According to these results, FISH performed on exfoliated urothelial ceils from urine has a sensitivity exceeding that of cytology, making the former a valuable noninvasive method for the diagnosis of patients with bladder cancer.