Clinical Application Study Of Fluorescence In Situ Hybridization In Urothelial Carcinoma And Prostate Cancer

Fluorescence in situ hybridization(FISH) is a kind of technology of non-radioactive in situ Hybridization, which was deVeloped on the basis of radioactiVe hybridization in the later 1980s. The fluorescence molecules were labeled to genetic material to obtain the probes. Probes have the ability to selectively block target gene according to base-pair complementary, and then the quantity and structure change of the hybridized chromosome could be observed by the fluorescence signal under fluorescence microscope. Because of the advantages of simple operation, safety, effective, high security and specificity, fluorescence in situ hybridization has widely been used in the detection of genetic disease, hematological malignancy, solid tumor and so on. With the rapid development of molecular genetics, some specific chromosome aberrat-ions have been often found in urothelial cell carcinoma and prostate cancer, laying theoretical foundation for the application of fluorescence in situ hybridizatio in urogenital cancers. This study is divided into three parts and the clinical application of fluorescence in situ hybridizatio in bladder urothelial carcinomas, upper tract urothelial carcinomas or prostate cancer was evaluated in this study respectively.Purpose To research the relations between aberrations of chromosome 3,7,17, p16 and bladder urothelial carcinoma, by the fluorescence in situ hybridization. To assess the clinical utility of fluorescence in situ hybridization as a non-invasive method in the diagnosis and postoperative follow-up of bladder urothelial carcinoma in Chinese group.Methods Urine samples of both 100 patients with bladder urothelial carcinoma and 30 non-cancer controls were analyzed by means of cytology and fluorescence in situ hybridization. Fluorescence in situ hybridization were used to detect the abnormalities of chromosome 3, 7,17 and p16. We compared the sensitivity and specificity between fluorescence in situ hybridization and cytology and analyzed whether the rates of abnormalities in chromosome 3,7,17, p16 have significant associations with tumor size, tumor number recurrence, clinical and pathologic tumor stages statistically. Bladder washings collected from 66 patients with non-muscle invasive bladder urothelial carcinomas three months after operation were analyzed by the fluorescence in situ hybridization to assess the role of fluorescence in situ hybridization in surveillance of recurring bladder cancer.Result The sensitivity of fluorescence in situ hybridization and cytology was 82% and 36%, and fluorescence in situ hybridization was significantly more sensitive than cytology (p< 0.001). The specificity of fluorescence in situ hybridization and cytology was 96%and 100%, and there was no significant difference between the two groups(p>0.05). The polysomic aberration rates were 63%(3),72%(7),31%(p16),60%(17); the monosomic aberration rates 53%(3),49%(7),47%(p16),46%(17); 34% presented a homozygous deletion of chromosome 9p21. There were no associations between abnormalities of chromosomes and tumor size, tumor number recurrence(p>0.05). The polysomic aberration rates of chromosome 17 were significantly associated with clinical and pathologic tumor stages(p< 0.05), while the other patterns of Chromosome aberrations were not(p>0.05). After a median follow-up of 22 months, 23 patients with non-muscle invasive bladder urothelial carcinomas developed tumor recurrence. The recurrence rate was significantly higher in patients with positive results of fluorescence in situ hybridization (54%) than in patients with negative results(13%) (p<0.001).Conclusions Fluorescence in situ hybridization assay of chromosomes 3,7,17 and p16 is an effective method to detect bladder urothelial carcinomas with with high sensitivity and specificity. FISH might contribute to not only an effective and invasive diagnostic approach to bladder urothelial carcinomas, but also an available tool for predicting tumor recurrence. Purpose To evaluate the possibility and validity of detecting the aberrations of chromosome 3,7,17and p16 by fluorescence in situ hybridization in order to diagnose upper tract urothelial carcinoma.Methods Urine samples of both 23 patients with upper tract urothelial carcinomas and 20 patients without urothelial carcinomas served as control group were analyzed by means of cytology and fluorescence in situ hybridization. The mixtures of fluorescent labeled probes to the centromeres of chromosomes 3,7 and 17, and p16 were used to detect chromosomal abnormalities. Sensitivity and specificity of both methods were determined and cpmpared.The utility of FISH in upper tract urothelial carcinomas were compared to the utility in bladder urothelial carcinomas through statistical analysis.Result The sensitivity of fluorescence in situ hybridization and cytology was 90% and 48%, fluorescence in situ hybridization was significantly more sensitive than cytology (p<0.001). The specificity of both methods wae 100%. The sensitivities of fluorescence in situ hybridization were no significant difference between upper tract urothelial carcinoma and bladder urothelial carcinoma.Conclusions The sensitivity of fluorescence in situ hybridization for the detection of upper tract urothelial carcinomas is superior than that of cytology whilst maintaining a similar specificity, fluorescence in situ hybridization might become a very useful tool in the diagnosis and differential diagnosis of upper tract urothelial carcinoma. Purpose To research the relations between fushion of TMPRSS2 and ETS transcription factor genes (ERG, ETV1, ETV4) and prostater caner, by the fluorescence in situ hybridization. To assess the clinical utility of fluorescence in situ hybridization in the diagnosis and differential diagnosis of prostater caner in Chinese group.Methods The prostate specimens including 53 prostate cancers,20 benign prostatic hyperplasias (BPH),5 high grade prostatic intrae-pithelial neoplasias (HGPIN) were separetely analyzed by means of fluorescence in situ hybridization to assess the gene fushions indiative of malignancy. The relationship between aberration of ERG gene and Gleason's scores, PSA and clinical stage was analysed respectively.Result Of 53 prostate cancer specimens,TMPRSS2/ERG fusion was detected in 32cases(60%); TMPRSS2/ETV1 fusion was detected in 5 cases(9%) and TMPRSS2/ETV1 fusion in 1 case(2%). 1case(20%) of HGPIN was detected with aberration of ERG gene. None of the three types of gene fushion was detected in all 20 cases of BPH. The sensitivity and specificity of FISH for the detection of prostate cancer was 72% and 96%. Aberration of ERG gene in prostate cancer was significantly associated with Gleason's scores and pathological stage(p<0.05), while not associated with PSA(p>0.05).Conclusions Fluorescence in situ hybridization assay is an effective method to detect prostate cancer with high sensitivity and specificity, contributing to improving the current diagnosis and differential diagnosis of prostate cancer. The gene fushions of TMPRSS2 and ETS transcription factor genes could be a new approach for the study on etiology of prostate cancer, and an important direction in treatment and prediction of the prognosis.