Comparison of ImmunoCyt,UroVysion, and urine cytology in detection of recurrent urothelial carcinoma

BACKGROUND:

ImmunoCyt (uCyt) and UroVysion are ancillary studies that may aid in the detection of urothelial carcinoma in urine specimens. We compared ImmunoCyt and UroVysion to urine cytology in the ability to detect recurrent urothelial carcinoma.

METHODS:

Single voided urine samples were obtained from 100 patients who had a previous history of bladder cancer. All patients underwent cystoscopy immediately after urine sample collection. Forty‐one cystoscopically suspicious lesions were biopsied. Urine samples were divided and processed blindly and independently in 3 different laboratories for ImmunoCyt, UroVysion, and urine cytology (ThinPrep method).

RESULTS:

Of the 41 cystoscopically positive cases, most cystoscopy findings showed multiple tumors that were papillary and less than 1 cm. Biopsies showed many low‐grade tumors (54%). Overall sensitivity of cytology for low‐ and high‐grade urothelial cell carcinoma was 15% and 27%, whereas ImmunoCyt was 62% and 91% and UroVysion was 8% and 18%, respectively. Overall specificity of cytology was 97%, whereas ImmunoCyt was 63% and UroVysion was 90%.

CONCLUSIONS:

ImmunoCyt is more sensitive than either cytology or UroVysion in detecting low‐grade tumors. Both cytology and UroVysion have comparable specificity in cystoscopically negative cases. Whereas ImmunoCyt may improve the cytological detection of recurrent bladder cancer, UroVysion may be used as a confirmatory test for either cytology or ImmunoCyt. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Fluorescence-in-situ-hybridization in the Surveillance of Urothelial Cancers: Can Use of Cystoscopy or Ureteroscopy be Deferred?

Background: Fluorescence in situ hybridization (FISH) testing may be useful to screen for bladder carcinomaor dysplasia by detecting aneuploidy chromosomes 3, 7, 17 and deletion of the chromosome 9p21 locus in urinespecimens. This study aimed to assess the sensitivity, specificity, positive and negative predictive value of FISHin a multi-ethnic population in Asia. Materials and Methods: Patients with haematuria and/or past history ofurothelial cancer on follow-up had their voided urine tested with FISH. Patients then underwent cystoscopy/ureteroscopy and any lesions seen were biopsied. The histopathological reports of the bladder or ureteroscopicmucosal biopsies were then compared with the FISH test results. Results: Two hundred sixty patients wererecruited. The sensitivity and specificity of the FISH test was 89.2% and 83.4% respectively. The positive (PPV)and negative predictive values (NPV) were 47.1% and 97.9%. By excluding patients who had positive deletionof chromosome 9, the overall results of the screening test improved: sensitivity 84.6%; specificity 96.4%; PPV75.9% and NPV 97.9%. Conclusions: UroVysion FISH has a high specificity of detecting urothelial cancer ordysplasia when deletion of chromosome 9 is excluded. Negative UroVysion FISH-tests may allow us to conservehealth resources and minimize trauma by deferring cystoscopic or ureteroscopic examination.     

A multicolor fluorescence in situ hybridization assay: A monitoring tool in the surveillance of patients with a history of non-muscle-invasive urothelial cell carcinoma: A prospective study

BACKGROUND:

Non–muscle‐invasive urothelial cell carcinoma (NMIUCC) has a high tendency to recur and affected patients must be monitored regularly using invasive cystoscopies. The aim of the current study was to compare a multicolor fluorescence in situ hybridization (FISH) assay (UroVysion) with routine follow‐up (cystoscopy and cytology) in the monitoring of patients with a previous history of NMIUCC.

METHODS:

An unselected cohort of patients under surveillance for a previous history of NMIUCC was prospectively studied. A total of 248 examinations in 223 patients were analyzed. Each exploration was comprised of cytological and FISH microscopic examination of voided urine samples and cystoscopy. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for tumor recurrence of all 3 techniques were determined.

RESULTS:

The sensitivities of FISH and cystoscopy were not found to be significantly different (92.9% and 82.1%, respectively). The specificities of FISH and cystoscopy were 92.7% and 89.7%, respectively. The PPV and NPV of FISH were 53.5% and 97.2%, respectively, whereas those of cystoscopy were 63.4% and 98.9%, respectively. No significant differences were found between these 2 tests. In contrast, the sensitivity and specificity of cytology were 14.3% and 99.5%, respectively.

CONCLUSIONS:

Given the lack of statistically significant differences with regard to FISH and cystoscopy results, the authors propose that FISH could be a useful monitoring tool in the surveillance of patients with a previous history of NMIUCC. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.     

Combined morphologic and fluorescence in situ hybridization analysis of voided urine samples for the detection and follow‐up of bladder cancer in patients with benign urine cytology

BACKGROUND.

Bladder cancer is among the 5 most common malignancies worldwide. Patients with bladder cancer are closely followed with periodic cystoscopies and urine cytology analyses due to the significant risk of tumor recurrence. The UroVysion fluorescence in situ hybridization (FISH) test demonstrated higher sensitivity over urine cytology in detecting bladder cancer by most comparative studies.

METHODS.

In the current study, the diagnostic usefulness of a combined cytology and FISH analysis approach was tested using the Duet automatic scanning system in patients with benign urine cytology who were being monitored for recurrent urothelial carcinoma or being assessed for various urologic symptoms.

RESULTS.

By combining the benefits of conventional cytology with molecular diagnostics, a more sensitive detection of bladder cancer was attained. All patients who had positive cystoscopy concomitantly with urine sampling were detected by combined analysis. Additional patients that developed transitional cell carcinoma during a follow‐up period of 24 months had a previous positive result on combined analysis. Only 2 patients with a negative combined analysis result presented with late disease recurrence (20 months and 22 months, respectively, after the negative test). Therefore, negative combined analysis was found to be predictive of a lack of disease recurrence for at least 12 months. In this timeframe, the overall sensitivity, specificity, negative predictive value (NPV), and positive predictive values of the combined analysis test were 100%, 65%, 100%, and 44%, respectively.

CONCLUSIONS.

Given the absolute sensitivity and NPV of the combined analysis test, the management of patients with a negative combined analysis result might be revised and allow for more flexible assessment and management of bladder cancer patients relying more on urine bound tests. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

Fluorescence in situ hybridization for detecting urothelial carcinoma

BACKGROUND:

Because urothelial carcinoma (UC) is associated with a significantly high risk of disease recurrence and progression, patients with UC require long‐term surveillance. Fluorescence in situ hybridization (FISH) has been shown to be more sensitive than cytology in the detection of UC. The current study evaluated the use of FISH for detecting UC.

METHODS:

A pathology database was used to identify patients who had urine cytology and FISH performed at the study institution between 2004 and 2006. Urinary specimens were analyzed using UroVysion FISH probes for abnormalities in centromeric chromosomes 3, 7, and 17 and locus‐specific 9p21. FISH results were correlated with cytologic findings and a minimal clinical follow‐up of 24 months.

RESULTS:

A total of 1006 consecutive urinary specimens from 600 patients (448 men and 152 women) who were monitored for recurrent UC (915 specimens) or evaluated for urinary symptoms (91 specimens) were identified. On FISH analysis, 669 specimens were found to be negative for UC and 272 specimens were positive for UC. Sixty‐five (6%) specimens were insufficient for FISH analysis. The sensitivity and specificity of FISH for UC were 58% and 66%, respectively, and 59% and 63%, respectively, when FISH and cytology results were combined. Factors contributing to decreased FISH sensitivity included the paucity or absence of tumor cells, low‐grade tumors, degenerated cells, method of specimen collection, type of specimen, and obscuring inflammatory cells or lubricant.

CONCLUSIONS:

UroVysion FISH appeared to have good sensitivity and specificity for detecting UC in urinary specimens. It is important to correlate the FISH results with the cytologic findings. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Value of p16(INK4a) in the diagnosis of low-grade urothelial carcinoma of the urinary bladder in urinary cytology

BACKGROUND:

The sensitivity of urinary cytology for the diagnosis of urothelial carcinomas is low, particularly in low‐grade carcinomas. The UroVysion test is a fluorescent in situ hybridization multiprobe assay that increases the sensitivity of urinary cytology. However, this test is not widely available. P16^INK4a, a protein involved in cell cycle progression, is overexpressed in urothelial carcinoma. Immunocytochemical expression of p16^INK4a has been examined in biopsy samples from urothelial carcinomas, but few studies have addressed this protein in urine cytology.

METHODS:

The authors compared the results of p16^INK4a immunoreactivity in cytology and biopsy samples from 83 cases, including low‐grade urothelial carcinomas, reactive epithelial lesions, and negative cases.

RESULTS:

p16^INK4a assessment of in urine cytology samples showed a sensitivity of 66.7% and a specificity of 82.8% in the diagnosis of low‐grade urothelial carcinomas.

CONCLUSIONS:

On the basis of these results, the authors propose that immunocytochemical detection of p16^INK4a is a reliable tool in urine cytology, both for the diagnosis of low‐grade urothelial carcinomas and for follow‐up purposes. More retrospective and prospective studies are required to verify these results. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.     

Evaluation of chromosomal aberrations in patients with benign conditions and reactive changes in urinary cytology

BACKGROUND:

Fluorescence in situ hybridization (FISH) is routinely used to help clarify atypical urinary cytology. However, to the authors' knowledge, little is known regarding the frequency of chromosomal aberrations in non‐neoplastic conditions that could potentially lead to false‐positive FISH results. The objective of the current study was to evaluate the frequency of chromosomal aberrations in benign cells of the urinary tract using the UroVysion FISH test.

METHODS:

The authors analyzed 77 Papanicolaou‐stained benign urine cytology specimens with reactive epithelial atypia using a FISH assay detecting the chromosomes 3, 7, and 17 and the gene locus 9p21. A positive test result was defined as an increased copy number of at least 2 chromosomes in ≥ 4 of 25 cells, or > 10 cells with a tetraploid or octaploid pattern, or homozygous or heterozygous deletion of 9p21 (≥ 12cells).

RESULTS:

FISH was positive in 27 of 77 bladder washings (35.1%) including 25 of 65 bladder washings (40.5%) and 2 of 15 voided urines (13.5%) from patients with irritative bladder (15 of 36 patients), a history of radiotherapy (7 of 12 patients), nonspecific cystitis (3 of 11 patients), hematuria (3 of 8 patients), and lithiasis (1 of 4 patients) . In 7 of 27 FISH‐positive urothelial specimens, the positivity was solely due a polyploid pattern (tetraploid/octaploid pattern) in > 10 of the cells.

CONCLUSIONS:

Chromosomal aberrations can occur in reactive urothelial cells, with a tetraploid pattern being the most common. Even an aneuploid pattern of FISH signals does not always prove malignancy because it rarely occurs in reactive urothelial cells. Correlation of FISH results with cytomorphology and patient history is crucial to avoid false‐positive diagnoses. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.     

Clinical evaluation of two consecutive UroVysion fluorescence in situ hybridization tests to detect intravesical recurrence of bladder cancer: a prospective blinded comparative study in Japan

Background

We evaluated the use of UroVysion fluorescence in situ hybridization tests to detect the intravesical recurrence of bladder cancer during follow-up after a transurethral resection of bladder tumor (TURBT).

Methods

In this prospective, blinded, comparative study, 486 patients treated by TURBT within the prior 2 years were registered at 12 centers. Urine cytology and UroVysion tests were performed once or twice at a central testing laboratory. For the patients with no suspicious findings of bladder cancer in the first analysis, the same examination set was repeated 3 months later as the second analysis. Totals of 468 and 399 patients were eligible for the first and second analyses, respectively. We determined the sensitivity and specificity of two consecutive UroVysion tests.

Results

Bladder cancers were identified in 44 patients at the first analysis. The UroVysion test had 50.0% (95% CI 35.2–64.8%) sensitivity and 72.4% (68.3–76.8%). Urine cytology had 4.5% (0.0–10.7%) sensitivity and 99.8% (99.3–100.0%) specificity. The concordant rate of the first and second UroVysion test results was 72% (kappa coefficient 0.157). Interestingly, the patients with two consecutive positive UroVysion test results had the highest cancer detection rate (14.8%), which is greater than those of the patients with a positive result in either (7.2%) or neither (1.2%) of the two tests at the 3-month follow-up.

Conclusions

The UroVysion test provided higher sensitivity than urine cytology to detect bladder cancer during post-TURBT follow-up. Two consecutive UroVysion tests might be a better indicator to predict intravesical recurrence.

     

NA cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident

BACKGROUND:

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to ¹³¹I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine‐needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown.

METHODS:

During the first screening cycle (1998‐2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.

RESULTS:

All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered “positive” or “negative,” the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%.

CONCLUSIONS:

Among children and adolescents who were exposed to ¹³¹I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations. Cancer (Cancer Cytopathol) 2009. Published 2009 by the American Cancer Society.     

The Performance of the Xpert Bladder Cancer Monitor Test and Voided Urinary Cytology in the Follow-up of Urinary Bladder Tumors

BackgroundCystoscopy in complement with urinary cytology represents the gold standard for the follow-up of patients with urinary bladder tumours. Xpert Bladder Cancer Monitor Test (XBC) is a novel mRNA-based urine test for bladder cancer surveillance. The aim of the study was to evaluate the performance of the XBC and voided urinary cytology (VUC) in the follow-up of bladder tumours.Patients and methodsThe XBC was performed on stabilized voided urine and VUC was performed on urine samples. The results were compared to cystoscopic findings and histopathological results after transurethral resection of the bladder lesion.ResultsFor the prediction of malignant histopathological result sensitivity, the specificity and negative predictive value were 76.9%, 9 7.5% and 93.0% for the XBC and 38.4%, 9 7.5% and 83.3%, respectively for VUC. For the prediction of suspicious or positive cystoscopic finding sensitivity, the specificity and negative predictive value were 75.0%, 95.2%, and 93.0% respectively for the XBC and 41.7%, 97.6%, and 85.4% for VUC. The sensitivities for papilary urothelial neoplasms of low malignant potential (PUNLMP), low- and high-grade tumours were 0.0%, 66.7% an d 100.0% for the XBC and 0.0%, 66 .7% and 42.9%, respectively for VUC.ConclusionsThe XBC showed significantly higher overall sensitivity and negative predictive value than VUC and could be used to increase the recommended follow-up cystoscopy time intervals. Complementing the XBC and voided urinary cytology does not improve performance in comparison to the XBC alone.Key words: cystoscopy, Xpert BC Monitor Test, urinary bladder neoplasm, voided urinary cytology     

Examination of Diagnostic Accuracy of UroVysion Fluorescence In Situ Hybridization for Bladder Cancer in a Single Community of Japanese Hospital Patients

Objective: UroVysion (Abbott Molecular, Inc., Illinois, USA) is based on multicolor fluorescence in situ hybridization(FISH). It has been used successfully in the USA following its Food and Drug Administration approval in 2001. However,the technology was not approved for use in Japan until 2017. Cystoscopy and urine cytology are the most frequentlyused examinations to detect bladder cancer in Japan, and there are only a few reports regarding the performance ofUroVysion. Therefore, the aim of this study is to examine the diagnostic accuracy of UroVysion FISH in Japanesepatients whose tumors are detected by cystoscopy before transurethral resection of bladder tumor (TURBT). Methods:From April 2018 to July 2018, a total of 40 patients who were diagnosed as having bladder tumors by cystoscopy, andtherefore underwent TURBT were registered in this study. One day before TURBT, urine cytology and UroVysionFISH were used in order to compare the accuracy with which they could detect bladder carcinoma, as confirmed bypathological results of TURBT. Results: The pathological results of TURBT showed urothelial carcinoma in 33 cases.Urine cytology showed positive results for 0 cases (0%), suspicious results for 10 cases (30.3%), and negative resultsfor 23 cases (69.7%). On the other hand, UroVysion FISH indicated 9 positive cases (27.3%) and 24 negative cases(72.7%). There were 19 cases of urothelial carcinoma (57.6%) that were not detected by either method. Conclusion:We conclude that UroVysion FISH alone is insufficient to detect bladder cancer and that cystoscopy is essential for theoptimum detection or follow up of bladder cancer cases in our hospital.     

Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine‐needle aspirates suspicious for Hurthle cell neoplasms

BACKGROUND:

Thyroid fine‐needle aspiration (FNA) samples that feature a follicular‐patterned, monotonous Hurthle (oncocytic) cell population cannot be diagnosed reliably. The authors of this report recently identified cyclin D3 overexpression on histologic sections of Hurthle cell carcinoma. In this study, they assessed the diagnostic value of cyclin D3 immunohistochemistry added to routine cytology.

METHODS:

Fifty‐one FNA samples that were suspicious for Hurtle cell neoplasia and that had histologic follow‐up (19 malignant cases) were examined. Cyclin D3 expression levels were evaluated in cell block preparations and were compared with levels of the closely related cyclin D1 protein.

RESULTS:

Greater than 25% positive cells were used as the cutoff point, as suggested by previous studies. Cyclin D1 and cyclin D3 were highly specific (100% for both) and fairly accurate (75% and 92%, respectively) in distinguishing between benign and malignant oncocytic lesions; the positive predictive value (PPV) for each was 100%. However, both cyclins D1 and D3 had low sensitivity (32% and 79%, respectively) and low negative predictive value (NPV) (71% and 89%, respectively). In contrast, by adopting balanced receiver operating characteristic‐derived positive cutoff values, cyclin D1 (≥6.5%) and cyclin D3 (≥7.5%) were found to be highly sensitive (100% for both) and accurate (90% and 94%, respectively); and the NPV was 100% for both. In contrast, cyclins D1 and D3 had low specificity (84% and 91%, respectively) and a low PPV (79% and 86%, respectively); however, these values improved in samples that were positive for both cyclins (sensitivity, 100%; specificity, 94%; PPV, 90%; NPV, 100%; and accuracy, 96%).

CONCLUSIONS:

Cyclin D3 increased the suspicion of malignancy in indeterminate oncocytic lesions; its diagnostic performance depended on the cutoff point used and was enhanced further when combined with cyclin D1. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Digitized microscopy in the diagnosis of bladder cancer: analysis of >3000 cases during a 7-month period

BACKGROUND:

Fluorescent in situ hybridization (FISH) analysis of urine samples has proven to be a valuable adjunctive test to urine cytology for both diagnosis and monitoring recurrence of urothelial carcinoma. Automated FISH analysis has the potential to improve laboratory efficiency and to reduce interobserver and intraobserver variability, resulting in more accurate, reproducible, assay performance.

METHODS:

A total of 3200 slides containing urine specimens, hybridized with the UroVysion Bladder Cancer Kit (Abbott Molecular, Des Plaines, Illinois), a 4‐probe set for chromosomes 3, 7, 17, and 9p21, was evaluated at Acupath Laboratories. The slides were analyzed over a 7‐month period, using the Ikoniscope ‐ oncoFISH bladder Test System (Ikonisys, New Haven, Connecticut).

RESULTS:

Analysis included the incorporation of a “flagging” system developed by Acupath Laboratories to identify cases, based on specific criteria, likely to benefit from further manual review. By using US Food and Drug Administration (FDA)‐cleared scoring criteria, 96.3% of the slides could be reported directly from the automated scan, requiring no manual review of the slide. For the remaining 3.7% of the samples (all of which were very hypocellular), a manual review of each slide subsequently allowed diagnoses to be successfully reported. The average scan time was 31.7 minutes, and the average slide scan review time was 8.3 minutes.

CONCLUSIONS:

This study demonstrated the value of an automated approach to the analysis of FISH slides, affording the benefit of high‐throughput while providing the user with the necessary images and tools to quickly and accurately report a case. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.     

The Role of Bladder Epicheck Test In Follow-Up of Patients with Non-Muscle Invasive Bladder Cancer

IntroductionEpiCheck is a new urinary test that analyses DNA methylation biomarkers in order to identify high-risk urothelial cancerMaterials and methodsA prospective single centre study was performed. We analysed Epicheck results in a population of 231 patients in follow-up for non-muscle invasive bladder cancer. The primary endpoint was to evaluate sensitivity and specificity of Epicheck in detecting any type of bladder cancer recurrence. The secondary endpoint was to evaluate specificity and sensitivity of Epicheck in patients with high-risk recurrence and in patients recently treated with endovesical therapy (< 3 months).ResultsNegative predictive value (NPV) for cytology was 83 % while for bladder Epicheck it was 89 %, while positive predictive value (PPV) was 67 % and 73 % for cytology and Epicheck respectively. Considering only high grade non muscle invasive bladder cancer the sensitivity of Epicheck was 91 % and for cytology was 81 %, specificity was 85 % and 83 % and negative predictive value of Epicheck outreached 96 % compared to 92 % of cytology. Among patients with an ongoing or recent endovesical treatment it appears that sensitivity of Epicheck was 88% % compared to 73 % of cytology, specificity was 97 % and 85 % and NPV was 92 % compared to 82 % for cytology.ConclusionThe EpiCheck (test showed very high diagnostic values, higher than the currently, gold standard. The test might clinically improve the BCa management in terms of, reduced number of inconclusive/suspicious reports of cytology and endoscopy, reduced number of further examinations, reduced associated patient and economic     

“FISHing” to detect urinary and other cancers

BACKGROUND:

The UroVysion Bladder Cancer Kit detects amplifications of chromosomes 3, 7, and 17, and the deletion of 9p21, by fluorescence in situ hybridization (FISH). Because manual interpretation of UroVysion FISH is time consuming and can be challenged by variable probe signal strengths and background labeling, the authors investigated an automated image analysis system to improve throughput, productivity, quality control, and accuracy.

METHODS:

The authors evaluated the interactive BioView Duet imaging system as an aid to UroVysion FISH interpretation in a 2‐armed, blinded comparison with manual screens of the same 135 consecutive cases. Manual and Duet‐assisted interpretations were compared with respect to concordance, reproducibility, and timing.

RESULTS:

Eighty‐one cases were interpreted as positive or negative with 94% concordance and a kappa value of 0.84 between manual and Duet‐aided interpretations. Three cases that ultimately were judged positive were detected with the aid of Duet but were missed with a manual screen. A final interpretation could not be given for≈25% of Duet‐scanned cases. Duet‐aided interpretation was highly reproducible for patient and control slides. Pathologist evaluation time per case was 4 minutes compared with 30 minutes for manual interpretation. Cytotechnologist involvement added 18 minutes for a total of 22 minutes, a savings of 8 minutes per case.

CONCLUSIONS:

Duet‐aided interpretations were at least equivalent to manual interpretations. The system permitted interactive review of abnormal cells and had the ability to evaluate the same cells for brightfield cytology followed by FISH. The image processing and analysis tools of the Duet system enhanced the morphology skills of cytology professionals in providing accurate interpretations. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Urinary tumor marker for urothelial cancer]

The urinary tumor markers BTA, BFP and NMP22 used for urothelial cancer in Japan are reviewed briefly. We also evaluate and compare the sensitivity and specificity of BTA, BFP and NMP22 with urine cytology in detecting bladder cancer in 24 of our patients. The results showed that the sensitivity with urine cytology, BTA, BFP and NMP22 was 37, 54, 66 and 62% respectively. The specificity of BTA, BFP and NMP22 with urine cytology was 100, 65, 60 and 70% respectively. The sensitivity with BTA, BFP and NMP22 for urothelial cancer was higher than that with urine cytology. However, all except for urine cytology showed high false positive rates (83-90%) for urinary tract infection. These markers may thus complement urine cytology, which has a low sensitivity for urothelial cancer. Quite possibly they could act as low-cost and useful tumor markers, which could in turn reduce the number of invasive cystoscopic examinations. However, considering their high false positive rates for benign disease such as urinary tract infection, we must acknowledge that an ideal urothelial tumor marker, which is simple, non-invasive, inexpensive and accurate with high sensitivity and specificity has yet to be developed.     

荧光原位杂交在尿路上皮癌诊断中的应用

目的：检测尿路上皮肿瘤患者尿液脱落细胞染色体的缺失和非整倍异常,探讨FISH技术作为尿路上皮肿瘤患者无创诊断方法的价值。方法：收集可疑尿路上皮肿瘤患者和健康对照人群的新鲜尿液,同步进行细胞形态学分析及荧光原位杂交（Fluorescence in situ hybridization, FISH） 检测3号、7号及17号染色体、9号染色体p16位点异常。共入选可疑尿路上皮肿瘤患者100例,正常健康对照组20例,采用正常对照组患者各染色体异常数据设定阈值用于肿瘤患者的实验室诊断。根据检验结果与病理结果对照分别计算FISH和脱落细胞的敏感度和特异度并进行统计学分析。结果：与正常对照组相比,尿路上皮肿瘤患者尿液脱落细胞染色体异常明显增多。尿脱落细胞学的敏感度和特异度分别为71%和80%,FISH的敏感度和特异度分别为88%和80%（P<0.01）。根据两种检测方法的敏感度和特异度绘制的接受者工作特征（ROC）曲线显示尿脱落细胞学和FISH的曲线下面积分别为0.758和0.842。结论：对可疑尿路上皮肿瘤的患者进行FISH检测是一种有价值的无创检测方法。FISH的总体敏感度高于尿脱落细胞学,特异度与尿脱落细胞学相当。     

Detection of bladder cancer from the urine using fluorescencein situ hybridization technique

The authors report on their first experiences with the UroVysion fluorescencein situ hybridization (FISH) kit developed for the detection of bladder cancer. This new non-invasive diagnostic application of the FISH technique in the field of urology was elaborated to replace cystoscopy. The special urine examination method detects genetic alterations of the urothelial cells found in the urine, using fluorescent directlabeled DNA probes binding to the peri-centromeric regions of chromosomes 3, 7 and 17 as well as on the 9p21 locus. We aimed to evaluate the utility of UroVysion test in the light of the histological diagnosis. Urine samples from 43 bladder cancer patients and 12 patients with no or benign alterations were studied using a new application of FISH technique: the UroVysion reagent kit. The obtained FISH results were compared with the histological findings of the transurethral surgical resection specimens. The study rated the specificity and sensitivity of the technique 100% and 87%, respectively. Therefore, the technique could well fit into the diagnostic process of bladder carcinomas. Statistical analyses showed significant correlation between tumor progression and the severity of the genetic alterations detected by this FISH technique. Furthermore, positive correlation was found between tumor grade and the proportion of tumor cells showing genetic abnormality. The noninvasiveness, the robustness of evaluation and the high specificity/sensitivity are all in favor of this technique. The disadvantages are the higher costs of the technical background and the required future clinical studies to determine whether this technique can replace cystoscopy. Both authors have equally contributed to this work. This work was supported by the following grants: NKFP-1A/0023/2002, OMFB 00606/2003     

DNA image cytometry and fluorescence in situ hybridization for noninvasive detection of urothelial tumors in voided urine

BACKGROUND: Cystoscopy and histologic examination remain the standard methods for initial tumor diagnosis and monitoring for early detection of recurrences, since the sensitivity of conventional urinary cytology for the detection of urothelial tumors in urinary specimens is low. DNA image cytometry (ICM) and fluorescence in situ hybridization (FISH) have been suggested as ancillary tools. The goal of the current study was to compare the diagnostic value of DNA image cytometry and FISH for the noninvasive detection of urothelial tumors in voided urine. METHODS: Cytospin preparations were prepared from voided urine collected prior to the resection of 26 noninvasive (pTa) and 11 invasive (pT1-2) tumors. Specimens from 14 patients with benign prostatic hyperplasia were used as negative controls. DNA ICM was performed using the AUTOCYTE trade mark cell analytical system on Feulgen-stained cytospin specimens. The commercially available UroVysion trade mark FISH multiprobe was used to analyze chromosomes 3, 7, and 17, and 9p21. RESULTS: The overall sensitivity of cytology improved from 24% to 54% and to 78% if supplemented by ICM or FISH, respectively. Image cytometry detected all invasive tumors (pT1-2), while FISH missed one; FISH identified 19 of 26 (73%) pTa tumors, while only 9 (35%) of these tumors were aneuploid by ICM. The results of ICM and FISH were concordant in 37 of 51 (72%) cases. CONCLUSIONS: The current study shows that both FISH and ICM can successfully be used as supplementary methods to detect the clinically most relevant group of invasive bladder carcinomas. However, UroVysion FISH is more sensitive in the detection of pTa tumors than ICM, as it recognizes individual chromosomal alterations that frequently prevail in urothelial tumors.     

A review of reporting systems and terminology for urine cytology

Urine cytology continues to play an important role in the diagnosis and management of urothelial carcinoma, a common cancer of adults with significant morbidity and mortality. Because of its high sensitivity for high‐grade urothelial tumors, including lesions that may be cystoscopically occult, urine cytology nicely compliments cystoscopic examination, a method that detects most low‐grade tumors. Over the decades, several reporting schemes for urine cytology have been published in the literature, each of which has relative strengths and weaknesses. Unlike cervical cytology, there has not been widespread acceptance and use of any particular reporting scheme for urine cytology studies. Thus, terminology and criteria for urine cytology reporting are not uniform among pathologists, which can frustrate clinicians and hinders interlaboratory comparisons. Cancer (Cancer Cytopathol) 2013;121:9–14 © 2012 American Cancer Society.