Fluorescence In Situ Hybridization In Urothelial Carcinoma And Prostate Cancer

Objectives:To evaluate the clinical utility of a Multiprobe FISH (fluorescence in situ hybridization, FISH) Assay in Voided Urine Specimens for the detection of Urothelial carcinomas (UC) comparing the results with those afforded by urinary cytology. Methods:Voided urine specimens from 241 patients who had Urothelial carcinomas,183 patients with bladder cancer and 58 consecutive patients with UUT(upper urinary trac) UC and 40 healthy controls were analyzed by means of cytology and FISH. FISH was performed using a mixture of fluorescent labeler DNA probes for the centromeric regions of chromosomes 3,7, and 17 and 9p21 region.Results 1.The normal range of FISH was blind by 20 health volunteers.2. Overall sensitivity of FISH for bladder cancer was 85.4%(145/158) and specificities of FISH was 90%(36/40). There was significantly difference between low grade and high grade tumors (P=0.002). However, there was no significantly difference between non and muscle-invasive bladder cancer (P=0.487). Urinary cytology affords an overall sensitivities of 41.1% (65/158) and specificities of 92.5%(37/40). Overall sensitivity of FISH was significantly higher than that of urine cytology (P= 0.0001). The positive values was no significantly of difference between the urine cytology and FISH(P=0.94), and the negative predictive values was significantly (P=0.02). The sensitivities of FISH and cytology were 71.1% and 24.4%(P<0.0001) in non muscle-invasive UUT, and were 81.8% and 48.9%(P=0.016) in muscle-invasive UUT. The sensitivities were 50% and 12.5%(P=0.027) in low grade cancers and 87.0% and 44.4%(P<0.01) in high grade tumors.Specificities for both FISH and cytology were similar results P=0.548. Of 58 patients with UUT UC, polysomies of chromosome 3,7 and 17 were observed in 52.3%,56.9% and 35.7%, respectively, and loss of the p16 gene in 27.3%.Conclusion:1. FISH assay of chromosomes 3,7,9, and 17 performed on exfoliated cells from voided urine specimens has greater sensitivity than cytology for detecting UUT-UC whilst maintaining a similar specificity.2. The sensitivities of FISH is significantly correlated to pathologic grade of UC, and With the increase in sensitivity to increased pathological grade. There is no correlated between the sensitivities of FISH and tumors stage.3. FISH has higher sensitivity for recurrent UC, and it could be useful for monitoring in the follow-up after surgery.4. The aberrations of chromosomes p16 is lower than of 3,7,17 chromosomes, and one of causes clould is relatively strict of normal range. Objective 1. To assess the feasibility and advantage of Systematic transperineal ultrasound guided template prostate biopsy.2. We analyzed genetic rearrangements between TMPRSS2 and ETS (ERG, ETV1 and ETV4) in prostate cancer, and evaluated the clinical utility of in patients treated with prostate biopsy detecting PCa by FISH (Fluorescence in situ hybridization), which of the probes of TMPRSS2-ERG, ETV1 and ETV4.Methods 1. In a prospective study, a total of 437 patients (33-86year old,mean age 70.4±14.35) who met the inclusion criteria underwent 11 regions systematic transperineal ultrasound guided template prostate biopsy. The median PSA level was 80.3±12.9612.96 ng/ml (range 0.2-5000ng/ml) and the mean prostate volume was 57.6±14.72ml (range 10-200ml).2. FISH was performed using a mixture of fluorescent labeler DNA probes for the TMPRSS2-ERG, ETV1 and ETV4 fusion. (1) 40 patients were identified by prostate pathology,who met the inclusion criteria underwent 11 regions systematic transperineal ultrasound guided template prostate biopsy. They was Experimental group and 20 patients of benign prostatic hyperplasia controls were analyzed by means of FISH. (2) We analyzed the fusion gene and the biological features of prostate cancer Gleason score, prostate volume, pTNM stage and PSA Levels.Results 1. Prostate cancer was detected in 168 of 486 (38.5%).2. Prostate needle biopsy rate and the parameters relationship:(1) Relationship with the areas:the positive rate of 1-11 areas was no significant difference, P=0.16. The mean positives for the cancer of regions 1-10 and region 11 (theapical region) were 35.6%vs.47.9% in patients whose PSA<20 ng/ml (P<0.05); (2)and prostate volume relationship:The positive rate was negatively correlated with prostate volume; (3) and PSA level of relationship:When PSA> 4ng/ml, the positive detection rate was positively correlated with PSA level, PSA<4ng/ml, the positive detection rate of PSA levels were not related; (4) The positives for cancer contained within the anterior (1,2,9,10) and posterior parts (4,5,6,7) were no insignificantly (P>0.05) in all patients. Incidence of gross in hematuria 29.7%(130/437), urinary retention rate 1.1%(5/437) after puncture 1 week, and no serious complication occurred during the procedure.3. In 40 patients, the prostate cancer positive rate of 80%(32/40) by FISH, in which TMPRSS2-ERG probe was 52.5%(21/40), TMPRSS2-ETV1 was 22.5%(9/40), TMPRSS2-ETV45%(2/40). Three probes in a positive, and the remaining two shall be negative. No repeat positive patients.4. The relationship between biological characteristics of prostate cancer and FISH:No significant association between the presence of the fusion gene and any clinical feature, such as Gleason score, prostate volume, pTNM stage and PSA Levels.Conclusions 1. Systematic transperineal ultrasound guided template prostate biopsy is accurate, and there is relevance between the rate of positive and Prostate volume, serum PSA level.2. Prostate carcinoma foci are more frequently localized in the apical region in patients with PSA<20 ng/ml.3. Systematic transperineal ultrasound guided template prostate biopsy has no serious complication occurred during the procedure.4. FISH probes can detect the fusion gene of prostate cancer in TMPRSS2-ERG, TMPRSS2-ETV1 and TMPRSS2-ETV4. There is are no significant difference between positive and negative group of FISH and the biological characteristics of prostate cancer, such as Gleason grade, prostate volume, clinical stage and the PSA level.5. FISH is expected to become a new powerful tool in early diagnosis of prostate cancer.