多色荧光原位杂交在膀胱癌诊断及监测中的意义

The Significance of Multicolor Fluorescence in Situ Hybridization in Diagnosis and Monitoring of Bladder Cancer

目的:探讨通过多色荧光原位杂交(multicolor fluorescence in situ hybridization,M-FISH)技术检测3、7、9、17号染色体数目畸变诊断膀胱移行细胞癌(bladder transition cell carcinoma,BTCC)的可行性和有效性。方法:采用3、7、17号染色体着丝粒探针和9p21区带探针对46例BTCC患者、15例非肿瘤患者和5例正常人尿液脱落细胞核行M-FISH检测,并同时行尿脱落细胞学(urinary cytological examination,UCE)检查,比较其敏感性和特异性,并分析各条染色体畸变与肿瘤恶性程度的相关性。结果:①M-FISH和UCE的灵敏度分别为73.9%(34/46)、47.8%(22/46),两者比较P<0.05;特异度分别为95.0%、100%,两者比较P>0.05。②MFISH在肿瘤临床分期T_a-T_1、T_2～T_(?)的阳性率分别为50.0%、84.4%;病理分级G_1、G_2、G_3的阳性率分别为42.9%、80.0%、100%,其阳性率与BTCC分级分期呈正相关(P<0.05)。③3、7、17号染色体在BTCC的畸变率分别为71.7%、73.9%、73.9%,其畸变率与肿瘤分期分级呈正相关(P<0.05)。9号染色体畸变率为56.5%,与分级分期无明显相关性(P≥0.05)。结论:使用M-FISH技术检测尿脱落细胞3、7、9、17号染色体数目畸变具有敏感度高、特异性强的优点,并具无创性,对BTCC的诊断具有重要的临床应用价值。

Objective：To evaluate the possibility and validity of detecting numerical aberration of chromosomes 3, 7, 9 and 17 by multicolor fluorescence in situ hybridization （M-FISH） in order to diagnose bladder transition cell carcinoma（BTCC）. Methods： Some volunteers were recruited as subjects, including 46 patients suffering from BTCC, 15 non-tumor patients, and 5 healthy individuals. Exfoliated cells from fresh urinary specimen was eollected and examined by M-FISH using centromeric probes of chromosome 3, 7, 17 and region probe of 9p21. Urinary cytological examination （UCE） was applied at the same time. The sensitivity and specificity of each method in the diagnosis of bladder cancer were determined and various chromosomal aberrations and malignant degree of correlation by comparative analysis. Results：（1） The sensitivity of M FISH and UCE were 73.9%, 47.8%, respectively. Comparison between the two（P〈0.05）, The specificity of M-FISH and UCE were 95.0%, 100% , respectively. Comparison between the two（P〉0.05） ,. （2） The positive rate of M-FISH in T0-T1 and T2-T4 patients were 50. 0% ,84.4%, respectively. The positive rate of M-FISH in G1 , G2, G3 patients Were 42.9%, 80.0%, 100%, respectively. The positive rate was positively associated with the clinical stage and pathological grade （P〈0.05）. （3） The frequency of numerical aberration of chromosomes 3, 7, 9,and 17 were 71.7% ,73.9%0,56.5%, and 73.9% in urinary exfoliated cells, respectively. Abnormality of chromosomes 3, 7and 17 was positively associated with the clinical stage and pathological grade（P〈0.05）, but aberration of chromosomes 9 was not correlated with pathological grade of cancer and stage of the disease （P≥0.05）. Conclusions：The sensitivity and specificity of M-FISH detecting 3, 7, 9, 17 chromosome aherrationns are high in the diagnosis of bladder cancer. It is a rapid, noninvasive, accurate and very sensitive method and can be used in clinical diagnosis and monitoring of post-operative patients.