N-myc gene amplification and other prognosis-associated factors in neuroblastoma

The correlation between N-myc gene amplification and heretofore known prognosis-associated factors was studied in 23 cases of neuroblastoma, comprising a total of 29 tumors (23 primary and six metastatic), examined in and after 1983. DNAs were extracted from tumor tissues preserved at -70 degrees C and digested with the restriction enzyme EcoRI. Southern blotting analysis was performed on these DNAs with the N-myc probe labelled with alpha-32P-dCTP. Prognosis-associated factors studied were age at diagnosis, stage, primary site, histological type, blood biochemistry tests, and catecholamine metabolites in urine. Amplification of N-myc gene was observed only in the cases in which primary site was the adrenal gland, but the relation to the stage, histological type, and prognosis was not as apparent as reported by other investigators. However, the amounts of catecholamine metabolites were low in the cases with amplification, and this suggests immaturity of catecholamine metabolism in the tumor with N-myc gene amplification.     

Surgical aspects of N-myc oncogene amplification of neuroblastoma

The surgical aspects of N-myc oncogene amplification of neuroblastic tumors were studied in 42 patients with ganglioneuroblastoma or neuroblastoma. The cumulative survival rate of patients with fewer than 10 copies of N-myc (L group) was 73.7% 48 months after initiation of therapy, whereas the rate for those with more than 10 copies of N-myc (H group) was 0% by 20 months (P less than 0.000001). Clinical prognostic factors of neuroblastic tumors such as age, stage, histologic findings, and primary site correlated with the amplification of N-myc. N-myc amplification of more than 10 copies was evident in one of 16 (6.3%) patients less than 1 year of age and in 13 of 26 (50%) patients over 1 year of age and was detected in one of six tumors in stage II, four of 10 in stage III, seven of 16 in stage IV, and two of six in stage IV-S. The amplification occurred more frequently in patients with neuroblastoma than in those with ganglioneuroblastoma and was observed only in tumors of a suprarenal region. Preoperative chemotherapy was prescribed for 19 of the 26 patients with stage III or IV tumors and was similarly effective in both L and H groups. Ipsilateral nephrectomy or combined resection of a part of liver had to be performed in nine of 11 (82%) patients with stage III or IV tumors in the H group but in only one of 15 (6.7%) in the L group, thereby suggesting that the tumor with an amplified N-myc is more invasive. In patients in the advanced stage, total or nontotal resection of the tumor did not affect the survival in the L group, but the survival interval was prolonged significantly by the total removal of the tumor in patients in the H group. These data should aid in the surgical treatment of patients with poor-prognostic neuroblastoma and an amplified N-myc oncogene.     

Improved survival for patients with advanced neuroblastoma after high-dose combined chemotherapy based in part on N-myc amplification

BACKGROUND/PURPOSE: In spite of many different kinds of chemotherapy for neuroblastoma, the prognosis for advanced neuroblastoma remains unsatisfactory. In particular, the outcome of advanced neuroblastoma with high copies of the N-myc gene tend to be poor. Therefore, the new high-dosage combined chemotherapy regimens for advanced neuroblastoma based in part on the N-myc amplification status has been utilized in the Kyushu area of Japan since 1991. This study aims to investigate whether these new regimens based in part on N-myc amplification have improved the survival rate of stage III and stage IV patients in comparison with the old regimens. METHODS: Between 1983 and 1995, 77 patients over 1 year of age and with stage III or IV neuroblastoma were registered in the Kyushu Area. Between 1983 and 1990, 49 patients received 1 of 2 combined chemotherapy regimens consisting of cyclophosphamide, cisplatin plus VM-26, and Adriamycin plus DTIC. Since 1991, two new regimens (New A1 and A3) have been administered based on the N-myc amplification status in a total of 28 patients. The New A1 regimen, which consists of cyclophosphamide, cisplatin, Adriamycin, and VP-16 has been administered in cases of less than 10 copies of N-myc, whereas the A3 regimen, consisting of a higher dose of cyclophosphamide, cisplatin, Adriamycin, and VP-16, has been administered in cases of more than 10 copies of N-myc. The survival rate was then compared between the old regimens and the new regimens. RESULTS: The 3-year survival rate (61.5%) for patients treated by the new regimens was significantly higher than that (32.7%) for patients treated by the old regimens (P <.01). Regarding the 24 cases of more than 10 copies of N-myc, the 3-year survival rate (35.9%) of the 13 patients treated by the A3 regimen was higher than that (0%) of the 11 patients treated by the old regimens (P <.05). However, in the 19 stage IV patients treated by the new regimens, the 3-year survival rate (11.1%) of the 9 cases of more than 10 copies was significantly lower than that (77.8%) of the 10 cases of less than 10 copies of N-myc (P <.01). CONCLUSIONS: These results suggest that high-dose combined chemotherapy based in part on the N-myc amplification status significantly improved the prognosis of patients with advanced neuroblastoma. However, stage IV patients with N-myc amplification still require a more effective treatment modality.     

N-myc oncogene amplification and prognostic factors of neuroblastoma in children

The N-myc oncogene of 28 neuroblastic tumors obtained from 16 untreated and 12 pretreated children was clinically evaluated and compared with known prognostic factors. Significant amplification of the N-myc (more than ten copies) was observed in 0 of 2 tumors in stage I, 1 of 5 in stage II, 2 of 6 in stage III, 6 of 9 in stage IV, and 2 of 6 in stage IVS. In stages II, III, IV, and IVS, all 15 patients with low N-myc amplification (under ten copies) are alive without disease, while among 11 patients with the amplification, seven died with progressive disease and two have a recurrence (P less than .01). All tumors with N-myc amplification originated from the suprarenal region and the amplification appeared in 55% of those from that origin. The amplification also correlated with the age factor. These results suggest that the genomic amplification of N-myc seems to be correlated with known prognostic factors of neuroblastoma, and may be a reliable factor even in the case of preoperatively treated tumors.     

Abnormal fluorescence in situ hybridization analysis in collecting duct carcinoma

Renal collecting duct carcinoma is a rare form of renal cancer known to present in a variety of ways that are often similar to presentations of renal cell carcinoma or transitional cell carcinoma. Little information is available concerning the use of cytology and fluorescence in situ hybridization (FISH) in the diagnosis of collecting duct carcinoma. The available literature contains cases with atypical cytology, but no collecting duct carcinoma cases with abnormal FISH results have been reported. We report a case of renal collecting duct carcinoma presenting with atypical cytology and abnormal FISH results.     

Inverse correlation between N-myc amplification and catecholamine metabolism in children with advanced neuroblastoma

The relationship between urinary excretion of catecholamine and/or its metabolites before the initiation of therapy and the genomic amplification of N-myc of the extirpated primary tumors was studied in 32 patients who had advanced neuroblastoma (stages III and IV). Values of vanillylmandelic acid, homovanillic acid, and noradrenaline excreted in urine were significantly higher in patients with 1 to 10 copies of N-myc (L-group) than in those patients who had more than 10 copies (H-group), whereas values of dopamine in urine were not significantly different between the groups. The ratio of urinary noradrenaline and dopamine was also significantly higher in the L-group. N-myc amplification, urinary excretion of vanillylmandelic acid and the noradrenaline/dopamine ratio significantly affected the prognosis. These data suggest that an inverse regulatory mechanism might be present between the N-myc amplification and catecholamine metabolism in patients who have advanced neuroblastoma, possibly at the level of gene and/or enzyme. These events would influence the prognosis. The main blockade of the metabolism may be in the metabolic processes from dopamine to noradrenaline.     

Immunohistochemical her-2/ Neu expression with gene amplification by fluorescence in situ hybridization for assessment in breast carcinomas

Objective: To compare gene amplification of HER-2/neu gene by fluorescence in situ hybridization (FISH) in moderate to strong immunohistochemically (IHS) positive HER-2/neu cases of invasive breast carcinomas. Study Design: Cross- sectional study. Place and Duration of study: Section of Histopathology, The Aga Khan University Hospital, Karachi, from January 2004 to December 2006. Patients and Methods: Forty one (41) diagnosed cases of invasive breast carcinomas were included in this study in which already determined immunohistochemical HER-2/neu expression was scored as either 2+ or 3+, based on the intensity of membranous staining. These cases were further evaluated for gene amplification by FISH. For gene amplification, a ratio of HER-2/CEP Z 2 was accepted as positive gene amplification. Results: Out of a total 41 cases, which were scored as 2+ and 3+ by IHC, 14 cases (34.1%; 95% confidence interval: 19%-49.3% ) showed gene amplification by FISH. Proportion of FISH positivity in IHC 2+ cases alone was found to be 25% (95% confidence interval: 10.5%-41%). In contrast, a majority of IHC 3+ cases (5 of 6) were positive by FISH studies. Conclusion: IHC is appropriate for initial HER-2/neu assessment and patients with tumors scored as 3+ may be treated alone based on this information provided strict quality control and 95% concordance with FISH assays; however, patients with tumors interpreted as 2+, would benefit from gene amplification by FISH studies for more accurate assessment to avoid inaccurate prognostication and treatment.     

Detection of C-erb B2 gene amplification in bilharzial associated bladder cancer using fluorescence in situ hybridization

BACKGROUND: Gene amplifications are common events in different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Fluorescence in situ hybridization (FISH) represents a standard methodologic approach for testing for this genetic alteration, as it is rapid, reproducible and extremely reliable in detecting presence of C-erb-B2 gene amplification for clinical utility. PATIENTS AND METHODS: In this study, FISH is used in a series of archival human bilharzial bladder cancer specimens to evaluate for the presence of cerbB-2 gene alterations in the most common malignant tumor in bilharzial endemic areas, e.g., Egypt and some other countries. The study included 40 cases, 30 males and 10 females. Their ages ranged between 30 years and 76 years (median: 51 years). Twenty-one cases had squamous cell carcinoma, 16 had transitional cell carcinoma, two had adenocarcinoma, and one case had undifferentiated carcinoma. RESULTS: Thirteen out of 40 tumor samples (32.5%) show evidence of true C-erb-B2 gene amplification. Of the remaining samples, 24 (60%) show no gene amplification and three (7.5%) fall into the borderline category with a ratio between one and two C-erb-B2 genes/cell relative to chromosome 17 centromeres. No evidence of chromosome 17 polysomy was found in any cases scored as single copy with the C-erb-B2 probe. CONCLUSION: No significant association was found between gene amplification and any of the tested clinicopathologic parameters or tumor recurrence except for tumor grade where higher tumor grades tended to be associated with more C-erb-B2 gene amplification (P = 0.01) thus reflecting more tumor aggressiveness. So, the amplification of C-erb-B2 in bilharzial associated bladder cancer is probably not independently related to clinical outcome of patients.     

应用荧光原位杂交技术检测骨肉瘤患者人表皮生长因子2受体基因扩增状态

目的 应用荧光原位杂交技术检测骨肉瘤人表皮生长因子2受体(HER-2/neu)基因是否存在扩增.方法 以HER-2/neu及17号染色体为探针,应用荧光原位杂交技术分析23例骨肉瘤病例HER-2/neu基因扩增情况,以HER-2/neu基因扩增阳性的乳腺癌病例作为阳性对照.结果 FISH检测23例骨肉瘤标本,无一例出现HER-2/neu基因扩增.结论 骨肉瘤中出现HER-2/neu基因扩增的频率极低,骨肉瘤患者可能不适合应用以HER-2/neu基因为靶点的靶向性药物.     

Cytogenetic analysis of gallbladder neoplasms using fluorescence in situ hybridization (FISH)

To characterize the numerical chromosome aberrations in gallbladder neoplasms, we examined surgically resected tissues using fluorescence in situ hybridization. The aberrations in 15 specimens of adenocarcinomas and 2 adenomas were compared with those in 4 samples of adenomyomatosis and 17 samples of normal epithelium. We calculated the frequency of aneusomy and determined the chromosome indexes (mean number of chromosomes per nucleus) of chromosomes 17 and 18. The pattern of DNA ploidy was analyzed by flow cytometry. In normal epithelium, adenomyomatosis and adenomas, DNA aneuploidy was not observed, while 13 (87%) carcinomas showed DNA aneuploidy, including 2 specimens with multiploidy. No numerical aberrations were observed in normal epithelium and adenomyomatosis. A numerical gain of chromosome 17 was observed in a single adenoma and in 10 (66%) carcinomas. A numerical gain of chromosome 18 was observed in 6 (40%) carcinomas, but not in other tissues. The chromosome index of chromosome 17 was significantly higher in adenomas and carcinomas (2.45±0.60 and 2.29±0.14, respectively) compared with normal epithelium. Our cytogenetic findings did not correlate with any histopathologic features of carcinomas. Our results indicated that the gains of chromosome 17 and 18 represented early chromosomal alterations in gallbladder neoplasms and were maintained in advanced carcinomas.     

Cytogenetic alterations in renal tumors. Applications for comparative genomic hybridization and fluorescence in situ hybridization

The WHO classification of renal cell carcinomas (RCC) takes into account chromosomal alterations. New cytogenetic techniques such as comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) offer alternative methods to the classic cytogenetic banding technique. Clear cell (classic) RCC frequently show the loss of 3p. Papillary RCC are characterized by trisomies and tetrasomies as well as loss of the Y chromosome. CGH analysis demonstrates that DNA copy increase is more common in type I papillary RCC compared to type II. Chromophobe RCC are characterized by losses in chromosomes 1, 2, 6, 10, 13, 17, and 21. Oncocytomas can be divided into cases with rearrangements in the 11q13 region and those with loss of chromosome 1 and the sex chromosomes. Translocations involving chromosome 3, such as t(3;8)(p14;q24.13) and t(2;3)(q35;q21) have been described in familial clear cell RCC. The most recent class of RCC, seen only in men, is referred to as translocation tumors. These tumors demonstrate a tubulopapillary growth pattern and have a t(X;1)(p11.2;q21.2) translocation. Although not required for most clinical diagnoses, CGH and FISH complement the standard histologic diagnosis of RCC and may provide a definitive diagnosis in a small number of challenging cases.     

多色荧光原位杂交在预测非肌层浸润性膀胱癌复发中的应用

目的 探讨荧光原位杂交(FISH)技术在判断膀胱癌复发的应用.方法 对20例正常人和51例非肌层浸润性膀胱癌患者术后行FISH检测,根据正常人检测结果建立阈值,分析膀胱癌患者FISH结果与膀胱癌复发的相关性.结果 平均随访21个月,22例患者发生肿瘤复发,其中FISH呈阳性19例(86%),呈阴性3例(14%);29例未复发FISH呈阳性16例(55%),呈阴性13例(45%).可见54%FISH检测阳性患者和19%FISH检测阴性患者出现了肿瘤复发.FISH检测呈阳性较呈阴性患者的膀胱癌复发概率大(P<0.05).结论 FISH在预测非肌层浸润性膀胱癌术后复发风险的判断中起重要作用.     

Monitoring intravesical therapy for superficial bladder cancer using fluorescence in situ hybridization

PURPOSE: We evaluated fluorescence in situ hybridization (FISH) for assessing the response to therapy in patients with superficial bladder cancer receiving bacillus Calmette-Guerin or other intravesical therapies. MATERIALS AND METHODS: A total of 37 patients receiving intravesical therapy for superficial bladder cancer were enrolled in this study. Urine specimens were collected for FISH analysis just prior to the first intravesical therapy in 31 cases and just prior to or within 2 months following the last intravesical therapy in 37. FISH was done using the UroVysion probe set (Abbott Laboratories, Abbott Park, Illinois) with results considered positive if 5 or more cells demonstrated polysomy. Biopsy, cystoscopy and/or cytology results were then compared to FISH results to evaluate the usefulness of the test for monitoring intravesical therapy. RESULTS: Of the patients 25 had a negative and 12 had a positive post-therapy FISH result. All 12 patients with a positive post-therapy FISH result had tumor recurrence, while tumor recurrence was observed in 13 of the 25 with a negative post-therapy FISH result (HR 4.6, 95% CI 1.9 to 11.1, p <0.001). Of the patients with tumor recurrence 7 of 12 with a positive post-therapy FISH result had muscle invasive tumor and 2 of 25 with a negative post-therapy FISH result had muscle invasive tumor (HR 9.4, 95% CI 1.9 to 45.3, p = 0.001). CONCLUSIONS: FISH appears to be useful for monitoring patients with superficial bladder cancer for the response to intravesical therapy. Patients with a positive FISH result at the end of treatment are at high risk for progression to muscle invasive bladder cancer.     

Urinary fluorescence in situ hybridization assay for detecting urothelial carcinoma in Taiwanese patients

Study Type – Diagnosis (case series)
Level of Evidence 4

OBJECTIVES

To investigate the cytogenetic marker detected by fluorescence in situ hybridization (FISH; UroVysion^TM, Vysis, Inc., Abbott Laboratories, Des Plaines, IL, USA) in the diagnosis of bladder cancer and upper tract urothelial carcinoma (UC) in Taiwanese patients, as FISH has been used in Western countries for detecting UC, but there are limited results in Asian populations.

PATIENTS AND METHODS

We analysed polyploidy of chromosome 3, 7, 17 and aneuploidy of chromosome 21, using uroepithelial cells collected at the first void or by instrumental extraction of urine, for bladder cancer, and shedding cells from the upper tract flushed by normal saline via ureteric catheterization or ureterorenoscopy. The criteria for positive tumour cells included three or more positive staining in two or more chromosomes showing polyploidy or <50% staining of the chromosome 9p21.

RESULTS

In all, 32 patients with bladder UC and 12 with upper tract UC were assessed. The overall sensitivity for bladder cancer by UroVysion was 96.8%. The sensitivity of the cytology test was 36% for UC of the bladder. The sensitivity for UroVysion in upper tract UC was 12/12 but the specificity was three of nine.

CONCLUSIONS

This preliminary report shows that UroVysion was a sensitive screening method for UC of the bladder and upper urinary tract.     

人精子间期核的双色荧光原位杂交

目的　建立人精子间期核双色荧光原位杂交 (dual colorfluorescenceinsituhybridization ,D FISH)的实验方法。方法　采用双色荧光原位杂交技术对 12例正常精子标本进行间期核的原位杂交 ,并统计精子间期核X、Y染色体的杂交信号颗粒数量。结果　在显微镜下可见精子头部有以Biotin标记的pBamX7探针显示 1个绿色杂交信号为X染色体精子 (X精子 ) ,以Digoxigenin标记的 pY3.4探针显示 1个红色杂交信号为Y染色体精子 (Y精子 ) ;精子头部有 2个荧光杂交信号的精子为染色体数目异常精子 (如XX、XY、YY精子 ) ;间期核背景经DAPI复染显示蓝色 ;统计 12例正常精子标本总共 4 80 0个精子间期核 ,X精子杂交信号阳性率为 4 8.5 6 % ,Y精子杂交信号阳性率为 4 9.73% ,总共统计 2 4 0 0 0个精子 ,3种双体总杂交率为 0 .197%。结论　本法具有荧光杂交信号直观易分辨、短时间内能大量分析精子数量和实验操作相对简便、结果准确可信等优点     

Analysis of parathyroid neoplasms by interphase fluorescence in situ hybridization

Recent studies have indicated that numerical chromosomal abnormalities, including changes in cyclin D1 and p53, may be involved in parathyroid tumorigenesis. We analyzed a series of parathyroid neoplasms with DNA fluorescent probes to evaluate the diagnostic and prognostic utility of numerical abnormalities of chromosomes 1, 6, 9, 11, 13, 15, 17, and 22 and cyclin D1 and p53 gene loci. Interphase fluorescence in situ hybridization (FISH) analysis was performed on paraffin-embedded tissue sections from 15 parathyroid adenomas and 18 parathyroid carcinomas. Directly labeled fluorescent DNA probes for the centromere region of chromosomes 1, 6, 9, 11, 15, and 17, and locus-specific probes for chromosome 22 and chromosome 13 and for cyclin D1 and p53 gene loci were used for dual-probe hybridization. Sixty-seven percent (10 of 15) parathyroid adenomas and 78% (14 of 18) of parathyroid carcinomas showed chromosome gains. Seventy-three percent (11 of 15) of parathyroid adenomas and 33% (6 of 18) of parathyroid carcinomas showed chromosome losses. Normal parathyroid tissues used as controls showed no chromosomal abnormalities. Parathyroid hyperplasias averaged 1.8 gains and 0.2 losses per case. Parathyroid adenomas averaged 2.8 gains and 0.8 losses per case, and parathyroid carcinomas averaged 3.6 gains and 0.6 losses per case. In summary, chromosome abnormalities, both gains and losses, are common in parathyroid adenomas and carcinomas. Parathyroid carcinomas tend to show gains of more chromosome than adenomas. Chromosome 11 was the most frequent chromosome loss identified in parathyroid adenomas and a frequent chromosomal gain in parathyroid carcinomas. These results indicate that gain of chromosome 11 is associated with more aggressive biologic behavior in parathyroid neoplasms.     

荧光原位杂交技术在膀胱尿路上皮癌诊断中的应用价值

目的 探讨荧光原位杂交技术(fluorescence in situ hybridization,FISH)在膀胱尿路上皮癌诊断中的应用价值. 方法 收集81例膀胱尿路上皮癌患者的新鲜尿液标本,分别行FISH和尿细胞学检测,并行膀胱镜检查;病理诊断泌尿系良性疾病12例合并8例临床诊断泌尿系良性疾病患者的尿液标本作对照.统计学分析FISH和尿细胞学检测诊断的特征值. 结果 81例均经病理检查确诊膀胱尿路上皮癌.非肌层浸润性膀胱尿路上皮癌34例,肌层浸润性癌14例;低级别42例,高级别24例;由于送检组织不完整,无法准确分期、分级者分别为33例和15例.FISH、尿细胞学和膀胱镜检查诊断膀胱尿路上皮癌的敏感性分别为72.8％ (59/81) 、27.2％ (22/81)和97.5％ (79/81),FISH诊断敏感性高于尿细胞学检测(P＜0.05),但低于膀胱镜检查(P ＜0.05);FISH和尿细胞学检测诊断特异性分别为85.0％(17/20)、100.0％ (20/20),二者比较差异无统计学意义(P＞0.05).FISH和尿细胞学检测诊断符合率分别为75.2％ (76/101)、41.6％(42/101),二者比较差异有统计学意义(P＜0.05). 结论 FISH检测诊断膀胱尿路上皮癌敏感性高、特异性强、无创,临床应用价值高.     

In situ hybridization analysis in IgA nephropathy

Summary: In situ hybridization provides much information on gene expression in renal biopsy specimens and is useful for detecting intrarenal cells producing molecules that are also present in the circulation. These molecules may deposit in the glomeruli. In situ hybridization is also useful for detecting cells producing cytokine that may be secreted immediately from such cells. Finally, in situ hybridization is useful for detecting extracellular matrix producing cells. Semiquantitative in situ hybridization is useful for assessing the retained RNA in the tissue and comparing the expression of specific mRNA in different tissues. This method may be useful in predicting the clinical outcome at the time of renal biopsy. In conclusion, in situ hybridization allows for the evaluation of cell function in human renal biopsy specimens. It not only provides information related to cell morphology, but also provides an estimation of functionality of human renal biopsy specimens.     

Immunohistochemical analysis of N-myc protein expression in neuroblastoma: correlation with prognosis of patients

We have analyzed N-myc gene amplification and N-myc protein expression in 41 primary neuroblastomas. In this series, 22 patients are currently alive and disease-free, whereas 19 patients have died or are alive with progressive disease. All tumor samples were obtained at operation. N-myc gene amplification was detected by Southern blot analysis, and N-myc protein expression was detected using Bouin-fixed, paraffin-embedded tissue sections and immunohistochemical staining with anti-N-myc gene products serum. N-myc protein expression was detected in all 9 tumors with N-myc gene amplification (greater than or equal to 10 N-myc gene copies). Among 19 patients with poor prognosis, N-myc gene amplification was detected in 8 (42%) and N-myc protein expression in 18 (95%); neither was detected in 20 of the 22 patients who survived free of disease. We conclude that the immunohistochemical detection of N-myc protein expression is one of the most unfavorable prognostic factors in neuroblastoma patients.     

荧光原位杂交技术在尿路上皮癌诊断中的应用

目的 探讨荧光原位杂交技术( FISH)在尿路上皮癌诊断中的应用价值.方法 采用FISH检测100例血尿患者尿脱落细胞中第3、7、17号染色体和第9号染色体p16位点异常,以组织病理学确诊尿路上皮癌为金标准,评估FISH诊断的敏感度和特异度,并与尿细胞学检查结果进行比较.结果 FISH检测和尿细胞学检查诊断尿路上皮癌的敏感度分别为82.5％和49.2％, 差异有统计学意义(P＜0.05)；特异度分别为86.7％和96.6％,差异无统计学意义(P＞0.05).结论 与尿细胞学比较,FISH诊断尿路上皮癌具有较高的敏感度和相似的特异度.