scholarly journals Biomarkers for detection and surveillance of bladder cancer

2013 ◽  
Vol 2 (3) ◽  
pp. 212 ◽  
Author(s):  
Lorne I. Budman ◽  
Wassim Kassouf ◽  
Jordan R. Steinberg

Introduction: Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer.Results: Sensitivity and specificity ranges, respectively, for each marker were reported as follows: BTA Stat (Polymedco), 52.5%–78.0% and 69.0%–87.1%; BTA Trak (Polymedco), 51%–100% and 73%–92.5%; cytology, 12.1%–84.6% and 78.0%–100%; hematuria dipstick, 47.0%–92.6% and 51.0%–84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%–100% and 60.0%–95.0%; NMP22 BladderChek (Matritech), 49.5%–65.0% and 40.0%–89.8%;ImmunoCyt/uCyt+ (DiagnoCure), 63.3%–84.9% and 62.0%–78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%–89.3% and 61.0%–77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%–100% and 65.0%–96.0%.Conclusion: We find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers, alone or in panel, would best accomplish this.

2005 ◽  
Vol 72 (4) ◽  
pp. 457-460
Author(s):  
P.F. Bassi ◽  
V. De Marco ◽  
C. Lamon ◽  
F. Longo ◽  
A. Volpe ◽  
...  

We evaluated the sensitivity and specificity of fluorescence in situ hybridization (FISH) performed on the urine specimens of patients under follow-up for superficial bladder cancer. Thirty-seven patients were enrolled and underwent cystoscopy, urinary cytology or biopsy and FISH examination. Urinary cytology and FISH were evaluated in exfoliated urothelial cells from bladder washings. A mixture of fluorescent labeled probes to the centromere of chromosomes 3, 7 and 17, and locus 9p21 was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. Nine patients (24.3%) showed an abnormal cystoscopy, but only five patients showed transitional cell carcinoma at histology. Eighteen patients (48.6%) showed an abnormal FISH: one patient (2.7%) had a positive cytology, and three patients (8.1%) showed an atypical cytology. Patients with both positive cystoscopy and histological examination had a positive FISH, while only one patient had a positive cytology. Patients with positive cystoscopy and negative histological examination had a negative FISH. Three patients with negative cystoscopy and suspicious cytology had a positive FISH. Ten patients (27%) with both negative cystoscopy and cytology had a positive FISH. The sensitivity of the FISH assay was 100%, 50% for the cytology and 62% for the cystoscopy. The specificity of the FISH assay, cytology and cystoscopy were 66%, 100% and 86%, respectively. The sensitivity of the FISH assay in detecting non-invasive urothelial tumors is worth further studies.


2001 ◽  
Vol 22 (3) ◽  
pp. 103-109 ◽  
Author(s):  
Bernhard Planz ◽  
Christian Synek ◽  
Thomas Deix ◽  
Alfred Böcking ◽  
Michael Marberger

DNA‐image‐cytometry and antibodies directed against the Lewis X‐ and the 486p 3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for the detection of bladder cancer. Cytology, immunocytology and DNA‐image‐cytometry were performed in spontaneously voided urine samples and barbotage bladder washings from 71 patients. The DNA content was determined using the CM‐1 Cytometer according to the recommendation of the ESCAP Consensus Report on Standardization of DNA‐image‐cytometry (1995). For immunocytological examination we used the monoclonal anti Lewis X antibody P‐12 and antibody 486p 3/12. All patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or transurethral resection was done. Histological findings revealed 31 patients with transitional cell carcinomas of different stages and grades of malignancy. 40 patients had various benign diseases of the urinary bladder. Cytology yielded a sensitivity of 68% and a specificity of 100%. DNA aneuploidy was detected in 81% of cancer patients with a specificity of 100%. By combination of these two methods the overall sensitivity increased to 87%. Immunocytology with Lewis X and 486p 3/12 antibodies showed reactivity in 84% and 87% in combination with a specificity of 80% and 70%, respectively. By combining urinary cytology, immunocytology and/or DNA‐image‐cytometry the overall sensitivity increased to 94% with no change in specificity. DNA‐image‐cytometry should be used to evaluate particularly urothelial cells suspicious for malignancy in urinary specimens. Because of low specificity the monoclonal antibodies against Lewis X‐ and 486p 3/12 antigens are not helpful in screening for bladder cancer. Nevertheless, their high sensitivity may justify their use in case DNA image cytometry is not available and in the follow up of patients with transitional cell carcinoma.


2018 ◽  
Vol 6 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Magdalena Bogdanovska-Todorovska ◽  
Slavica Kostadinova-Kunovska ◽  
Rubens Jovanovik ◽  
Blagica Krsteska ◽  
Goran Kondov ◽  
...  

BACKGROUND: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.MATERIAL AND METHODS: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti–HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.RESULTS: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.CONCLUSION: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.


2000 ◽  
Vol 46 (5) ◽  
pp. 595-605 ◽  
Author(s):  
Martin Burchardt ◽  
Tatjana Burchardt ◽  
Ahmad Shabsigh ◽  
Alexandre De La Taille ◽  
Mitchell C Benson ◽  
...  

Abstract Background: Transitional cell carcinoma of the bladder (TCC) is the second most common malignancy of the urinary tract. More than 70% of treated tumors recur, and 30% of recurrent tumors progress. Currently, pathologic staging and grading are valuable prognostic factors for detecting and monitoring TCC. Urinalysis, cystoscopy, and cytology are either invasive or lack sensitivity and specificity. The availability of a noninvasive, reliable, and simple test would greatly improve the detection and monitoring of patients with TCC. Several biomarkers for bladder cancer have been proposed, but no single marker has emerged as the test of choice. Approach: We undertook a comprehensive literature search using Medline to identify all publications from 1980 to 1999. Articles that discussed potential biomarkers for TCC were screened. Only compounds that demonstrated high sensitivity or specificity, significant correlation with TCC diagnosis and staging, and extensive investigation were included in this review. Content: Potential biomarkers of disease progression and prognosis include nuclear matrix protein, fibrin/fibrinogen product, bladder tumor antigen, blood group-related antigens, tumor-associated antigens, proliferating antigens, oncogenes, growth factors, cell adhesion molecules, and cell cycle regulatory proteins. The properties of the biomarkers and the methods for detecting or quantifying them are presented. Their sensitivities and specificities for detecting and monitoring disease were 54–100% and 61–97%, respectively, compared with 20–40% and 90% for urinalysis and cytology. Summary: Although urine cytology and cystoscopy are still the standard of practice, many candidate biomarkers for TCC are emerging and being adopted into clinical practice. Further research and better understanding of the biology of bladder cancer, improved diagnostic techniques, and standardized interpretation are essential steps to develop reliable biomarkers. It is possible that using the current biomarkers as an adjuvant modality will improve our ability to diagnose and monitor bladder cancer.


Author(s):  
Richard P. Meijer ◽  
Alexandre R. Zlotta ◽  
Bas W.G. van Rhijn

High-grade non-muscle-invasive bladder cancer (HG-NMIBC) represents the most aggressive spectrum of this non-invasive cancer. This collective term includes all high-grade NMI urothelial carcinoma (UC), such as those without invasion (pTa), those with lamina propria invasion (pT1), and those that are only/have concomitant carcinoma in situ (CIS; pTis). These cancers have a high risk for intravesical recurrence (around 46–78% at five years) and progression (between 6–45% at five years) to muscle-invasive bladder cancer (MIBC). As with all UC, their presentation can be with visible haematuria or irritative lower urinary tract symptoms. The latter are common in patients with CIS. CIS may be detected in isolation (so-called primary CIS) or with a coexisting UC elsewhere (termed concomitant CIS). While urinary cytology has a moderate sensitivity and high specificity (>90%) for the detection of HG-NMIBC, cystoscopy is the most important diagnostic tool.


1993 ◽  
Vol 60 (4) ◽  
pp. 345-348
Author(s):  
V. Serretta ◽  
S. Piazza ◽  
C. Pavone ◽  
G. Corselli ◽  
B. Piazza ◽  
...  

The Authors present their experience with TUR plus adjuvant intravesical chemotherapy in 50 patients affected by primary T1 G3 bladder tumours without previous or concomitant carcinoma in situ. At a mean follow-up of 36 months, 84% of the patients are alive and tumour-free. Cystectomy was performed in three patients due to locally invasive disease. Five patients (10%) died of bladder cancer.


2005 ◽  
Vol 72 (3) ◽  
pp. 301-306
Author(s):  
M. Ciaccia ◽  
R. Bertoloni ◽  
F. Pinto ◽  
A. Calpista ◽  
P.F. Bassi

Urine cytology is a reliable and well known tool in the diagnosis and follow-up of patients with transitional cell carcinoma even if it has high sensitivity only in high grade tumors and carcinoma in situ. In order to improve sensitivity of this test in patients with low grade tumors, new methods such as cytometry, microsatellite assays, Immunocyt®, fuorescence in-situ hybridization and Thin-Prep monolayer have been developed. These new assays will be able to increase the cytology detection rate and to predict the outcome of transitional cell carcinoma.


2009 ◽  
Vol 12 (3) ◽  
pp. 195-199 ◽  
Author(s):  
Naim K. Fanaian ◽  
Cynthia Cohen ◽  
Sandra Waldrop ◽  
Jennifer Wang ◽  
Bahig M. Shehata

Detection of Epstein-Barr virus (EBV) may be achieved by various methods, including EBV-encoded RNA (EBER) in-situ hybridization (ISH) and immunohistochemistry (IHC) for latent membrane protein (LMP-1). We compared novel automated ISH and IHC techniques in pediatric lymphoproliferative disorders with results obtained by manual ISH. Thirty-seven pediatric cases previously studied by manual EBER ISH (including 18 EBER-positive, 15 EBER-negative, and 4 EBER-equivocal cases) were used for the study. Automated EBER ISH and automated LMP-1 IHC were performed using the BondMax autostainer and prediluted EBER probe and EBV cell surface 1 to 4 at 1:50 dilution, respectively. Results of each of the automated techniques for EBV detection were compared with results by manual EBER ISH. Compared with manual EBER ISH as the gold standard, automated ISH had a sensitivity and specificity of 94% and 69%, respectively, accuracy of 83%, positive predictive value (PPV) of 79%, and negative predictive value (NPV) of 90%. Automated IHC had a sensitivity of 44%, specificity of 93%, accuracy of 67%, PPV of 88%, and NPV of 59%. Automated ISH and IHC correlated significantly ( P < 0.045). Automated ISH is useful for diagnosis of EBV-related pediatric neoplasms, being easy to perform and interpret and requiring only the technologist's time to set up and having a high sensitivity and NPV. The automated IHC protocol is of too low sensitivity for routine use, although results show high specificity and PPV.


Author(s):  
Kyohei Hakozaki ◽  
Eiji Kikuchi ◽  
Koichiro Ogihara ◽  
Keisuke Shigeta ◽  
Takayuki Abe ◽  
...  

Abstract Background Prophylactic urethrectomy at the time of radical cystectomy is frequently recommended for patients with bladder cancer at a high risk of urethral recurrence without definitive evidence. The present study attempted to clarify the survival benefits of performing prophylactic urethrectomy. Methods We identified 214 male patients who were treated by radical cystectomy with an incontinent urinary diversion in our seven institutions between 2004 and 2017. We used propensity score matching and ultimately identified 114 patients, 57 of whom underwent prophylactic urethrectomy (prophylactic urethrectomy group) and 57 who did not (non-prophylactic urethrectomy group). Results No significant differences were observed in the 5-year overall survival rate between the prophylactic urethrectomy and non-prophylactic urethrectomy groups in the overall. However, the local recurrence rate was significantly lower in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.015). In the subgroup of 58 patients with multiple tumours and/or concomitant carcinoma in situ at the time of transurethral resection of bladder tumour, the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.021). A multivariate analysis revealed that performing prophylactic urethrectomy was the only independent predictor of the overall survival rate (P = 0.016). In those patients who were treated without neoadjuvant chemotherapy (n = 38), the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.007). Conclusions Prophylactic urethrectomy at the time of radical cystectomy may have a survival benefit in patients with multiple tumours and/or concomitant carcinoma in situ, particularly those who do not receive neoadjuvant chemotherapy.


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