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.     

尿细胞角蛋白检测与尿脱落细胞学检查在膀胱癌诊断中的价值

目的:探讨尿细胞角蛋白检测与尿脱落细胞学检查在膀胱移行细胞癌诊断中的价值。方法:136例怀疑膀胱癌者,进行尿细胞角蛋白8和18的含量(UBC值)。检测与尿细胞学检查,其中87例经组织学证实为膀胱移行细胞癌。比较两者诊断膀胱癌的敏感性和特异性。结果:尿细胞角蛋白的敏感性为70.1%,特异性为73.3%;尿细胞学的敏感性为42.5%,特异性为83.7%。尿细胞角蛋白在膀胱癌不同分级和分期中的敏感性优于尿细胞学(P<0.05)。结论:尿细胞角蛋白的检测在早期诊断膀胱癌方面优于尿细胞学检查,可作为膀胱癌的早期检测指标。     

Diagnosis of genito-urinary tract cancer by detection of minichromosome maintenance 5 protein in urine sediments

BACKGROUND: Because cystoscopy is invasive and expensive and urine cytology has low sensitivity, alternative methods for detecting bladder cancer are sought. Minichromosome maintenance (Mcm) proteins have been used as diagnostic markers for cervical cancer. We investigated whether one Mcm protein, Mcm5, can be used to detect urothelial cancer cells in urine sediments. METHODS: We used two monoclonal antibodies against His-tagged human Mcm5 (amino acids 367-582) in an immunofluorometric assay to measure Mcm5 levels in cells in the urine of 353 patients who presented with hematuria or lower urinary tract symptoms or who were undergoing follow-up cystoscopy for urothelial neoplasia. Urine samples were also subjected to routine cytologic analysis. Patients underwent upper urinary tract imaging and cystoscopy within 12 hours of producing the urine sample. Data were analyzed by comparing areas under a nonparametric receiver operating characteristics (ROC) curve and by McNemar's test and Fisher's exact test. All statistical tests were two-sided. RESULTS: At the assay cut point where the false-negative and false-positive rates were the same, the Mcm5 test detected primary and recurrent bladder cancers with 87% (95% confidence interval [CI] = 77% to 94%) sensitivity and 87% (95% CI = 83% to 91%) specificity. At the cut point where the specificities of urine cytology and the Mcm5 test were equal (97%, 95% CI = 95% to 99%), the Mcm5 test was statistically significantly (P<.001) more sensitive than urine cytology, 73% (95% CI = 61% to 83%) versus 48% (95% CI = 35% to 60%). At the lower detection limit of the Mcm5 test, sensitivity was highest, 92% (95% CI = 83% to 97%) and specificity was 78% (95% CI = 72% to 83%). Patients with prostate cancer had higher levels of Mcm5 in their urine sediments than did men without malignancy (P<.001). CONCLUSIONS: Elevated levels of Mcm5 in urine sediments are highly predictive of bladder cancer.     

尿液检查在膀胱癌诊断和术后复发监测中的现状及进展

膀胱癌是我国男性泌尿生殖系统肿瘤中的最常见肿瘤.膀胱镜检查是诊断和治疗后随访的最主要手段,但其往往会带给患者痛苦和恐惧.无创性的尿液检查替代膀胱镜诊断膀胱癌、监测复发及判断预后,一直是研究的热点.除尿细胞学外,目前通过尿液检查诊断和监测膀胱癌复发主要有尿核基质蛋白22、膀胱肿瘤抗原、免疫-细胞检查法、纤维素和纤维蛋白降解产物及荧光原位杂交技术等方法,但敏感性和特异性均不十分理想.检测尿液的端粒酶、透明质酸和透明质酸酶的方法其敏感性和特异性较好,但尚未经多中心的研究证实.对膀胱癌尿液中新的肿瘤标志物的初步研究结果表明,微卫星体异常、一些基因启动子的异常甲基化、细胞角蛋白、survivin等在膀胱癌的诊断中有较大的应用价值,但目前这些方法均有其局限性.合理地联合应用上述无创性尿液分析手段,可望推迟或减少膀胱镜检查,但尚难以取代膀胱镜.     

Genomic profile of urine has high diagnostic sensitivity compared to cytology in non‐invasive urothelial bladder cancer

Cytology is widely conducted for diagnosis of urothelial bladder cancer; however, its sensitivity is still low. Recent studies show that liquid biopsies can reflect tumor genomic profiles. We aim to investigate whether plasma or urine is more suitable for detecting tumor‐derived DNA in patients with early‐stage urothelial bladder cancer. Targeted sequencing of 71 genes was carried out using a total of 150 samples including primary tumor, urine supernatant, urine precipitation, plasma and buffy coat from 25 patients with bladder cancer and five patients with cystitis and benign tumor. We compared mutation profiles between each sample, identified tumor‐identical mutations and compared tumor diagnostic sensitivities between urine and conventional cytology. We identified a total of 168 somatic mutations in primary tumor. In liquid biopsies, tumor‐identical mutations were found at 53% (89/168) in urine supernatant, 48% (81/168) in urine precipitation and 2% (3/168) in plasma. The high variant allele fraction of urine was significantly related to worse clinical indicators such as tumor invasion and cytological examination. Although conventional cytology detected tumor cells in only 22% of non‐invasive tumor, tumor diagnostic sensitivity increased to 67% and 78% using urine supernatant and precipitation, respectively. Urine is an ideal liquid biopsy for detecting tumor‐derived DNA and more precisely reflects tumor mutational profiles than plasma. Genomic analysis of urine is clinically useful for diagnosis of superficial bladder cancer at early stage.     

Clinical application of NMP22 in the management of transitional cell carcinoma of the bladder

The combination of a noninvasive, quantitative immunoassay, NMP22, with voided urinary cytology prior to cystoscopy was evaluated in patients with urothelial transitional cell carcinoma. Fifty-six patients with a history of transitional cell carcinoma were evaluated. Voided urine was obtained for NMP22 and cytology prior to cystoscopy. One hundred and twenty-three NMP22 assays, 124 cytologies, and 124 cystoscopies were performed. The type of anesthesia used for cystoscopic evaluation was determined by the NMP22 value in 30 patients. Cystoscopy results were considered positive on biopsy-confirmed malignancy. The reference value used for NMP22 was 10.0 U/ml. NMP22, cytology, and the combination of NMP22 and cytology were compared to cystoscopy and to pathologic grading and staging. Thirty-four recurrent transitional cell carcinoma episodes occurred; 22 were low-grade (I-II), and 12 were high-grade (III-IV). Twenty-seven were stage Ta; four were T1; and three were T3b or 4. Within this group, NMP22 detected low- and high-grade tumors equally, as compared to cytology, which was sensitive only to high-grade tumors. Nineteen patients were NMP22-negative and underwent cystoscopy under topical anesthesia; 17 were tumor-free. Eleven patients were NMP22-positive and had anesthesia, and all had visible lesions, which were subjected to biopsy and were resected. Six lesions were tumors, five were inflammatory. Overall sensitivity of combined NMP22 and cytology was 70%; specificity was 72%; positive predictive value was 54%; and negative predictive value was 77%. An accurate assessment of the risk of a bladder cancer can be obtained with NMP22, cytology, and cystoscopy in patients with a history of bladder cancer. NMP22 values can be used to determine the level of anesthesia for cystoscopy in patients with a history of bladder cancer.     

应用荧光原位杂交技术检测膀胱癌的研究

目的应用荧光原位杂交((fluorescence in situ hybridization,FISH)技术检测膀胱癌患者尿液脱落细胞中染色体异常,评估FISH在中国人群中诊断膀胱癌的作用。方法2007年1月至2008年8月,随机留取20例良性前列腺增生症患者的新鲜尿液,用3号和7号、17号及p16位两组混合探针,通过在尿液脱落细胞标本上进行FISH检测,建立正常人群的阈值;其后随机留取30例门诊膀胱镜活检证实的膀胱癌患者的尿液,同时进行尿液脱落细胞的细胞形态学分析及FISH检测,对比检查结果。结果3号、7号和17号染色体非整倍性改变及p16位点异常正常阈值分别为8.5%、7.1%、6.8%和9.2%,FISH与细胞学检查总敏感性分别为76.6%和43.3%(P<0.05)。T_(is)及T_a、T_1患者FISH检测的敏感性分别为80.0%和64.2%,脱落细胞组织学检测显示敏感性分别为40.0%和35.7%;T_(2-3)患者FISH的敏感性为90.9%,而脱落细胞组织学检测为54.7%(P<0.05),低级别尿路上皮癌FISH及细胞学敏感性分别为68.4%和31.6%;高级别分别为90.9%和63.6%。结论与尿液脱落细胞组织学检测相比,对尿液脱落细胞进行FISH检测可以提高膀胱癌的诊断率,FISH可以作为诊断膀胱癌的一种无创伤的新方法。     

Comparison of NMP22 BladderChek test and urine cytology for the detection of recurrent bladder cancer

OBJECTIVE: To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. METHODS: A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. RESULTS: Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. CONCLUSION: The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.     

Diagnostic and prognostic role of urinary collagens in primary human bladder cancer

Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin‐19 (CYFRA21‐1), nuclear matrix protein 22 (NMP‐22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21‐1, and NMP‐22 in urine supernatants were measured using enzyme‐linked immunosorbent assays. Diagnostic performance and optimal cut‐off values were determined by receiver operating characteristic analysis. Urine levels of COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1 + COL13A1), and CYFRA21‐1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cut‐off value of COL4A1 + COL13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low‐grade tumors, high‐grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non‐muscle invasive BCa samples after the initial transurethral surgery. A high urinary COL4A1 + COL13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. This easy‐to‐use urinary signature identifies a subgroup of patients with a high probability of recurrence and progression in non‐muscle invasive and muscle invasive BCa.     

荧光原位杂交和尿细胞学检查对膀胱癌诊断意义的Meta分析

背景与目的：目前膀胱癌疗效和监测的主要方法是膀胱镜和尿细胞学检查,前者为侵人性检查,令患者感到不适;后者虽无创且特异性高．但敏感性太低,且受主观因素影响大。本研究拟对中、英文有关比较荧光原位杂交（fluorescence in situ hybridization,FISH）和尿细胞学检查诊断膀胱癌研究的结果进行系统分析,以明确FISH对膀胱癌的诊断意义。方法：采用Cochrane系统评价方法,MEDLINE（1966年1月～2008年6月）、EMBASE（1988年1月。2008年6月）、Cochrane图书馆、中国生物医学期刊文献数据库（CMCC,1979年。2008年6月）、CNKI数字图书馆（1979年1月～2008年6月）进行有关FISH和尿细胞学检查诊断膀胱癌文献的检索、质量评价和资料提取,采用MetaDiScl．4软件进行Meta分析。结果：共检索到相关研究242篇,排除230篇,符合纳入标准12篇进入Meta分析,涉及研究对象3430例。异质性检验提示无阈值效应,但存在其它原因导致的异质性。按随机效应模型进行Meta分析．FISH和尿细胞学诊断膀胱癌的准确度指标敏感度、特异度、阳性似然比、阴性似然比以及诊断优势比等汇总及95％C1分别为74％（71％-77％）VS．57％（54％-61％）、88％（86％-90％）VS．85％ （83％-87％）、6．18（3．56～10．73）VS．4．15（2．78～6．20）、0．29（0．19～0．45）VS．0．51（0．41～0．63）及24．17（9．33～62．64）VS．9．59（5．91～15．57）。FISH和尿脱落细胞学检查的敏感度随肿瘤分级、分期的升高而增高。综合受试者工作特征曲线下面积分别为0．8938、0．8247．Q^＊值分别为0．7847、0．7226。结论：FISH诊断膀胱癌的准确度较高,但对高分期的敏感度较细胞学低,目前尚不能取代传统的尿细胞学检查,但可作为膀胱癌术前诊断、术后监测和随访的指标。     

BTA检测在膀胱癌诊断中的价值

目的BTA检测与尿脱落细胞学检查结果比较,以明确在膀胶癌诊断中的应用价值.方法 收集1996年12月～1997年1月经膀胱镜及病理学检查确诊为膀胱乳头状移行细胞癌的病人共47例.每一例于膀胱镜检查前连续留取三次晨尿,行尿脱落细胞学检查.最后一次标本同时行BTA检测及尿液常规化验.结果BTA检测膀胱癌的敏感度为70.2%(33/47),尿脱落细胞学检查敏感度为25.5%(12/47),两者有非常显著性差异(P<0.001).共有8例(17.0%)患者两种检查结果均为阳性,10例(21.3%)患者两种检测结果均为阴性.另外,BTA检测对T1期膀胱癌患者的敏感度明显高于尿脱落细胞学检查,其结果分别为76.0%(19/25)和12.0%(3/25),统计学分析示有非常显著性差异(P<0.01).结论 BTA检测是一种有价值的膀胱癌诊断辅助措施,且使用方便,检测迅速,无创伤性,便于临床开展.     

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.     

联合检测UBC、HA和CK20诊断膀胱癌的临床价值

背景与目的:膀胱癌是最常见的泌尿系统肿瘤,尿脱落细胞学检查是无创性诊断的金标准,但敏感性较低.本研究探讨联合运用尿膀胱癌抗原(urinary bladder cancer,UBC)、透明质酸(hyaluronic acid,HA)和细胞角蛋白20(cytokeratin 20,CK20)诊断膀胱癌的临床价值.方法:对64例膀胱癌患者、20例泌尿系良性疾病患者,在膀胱镜检查之前留尿,分别采用酶链免疫吸附实验、放射免疫分析和逆转录聚合酶链反应检测UBC、HA和CK20在尿液中的表达,同时行脱落细胞学检查,分析比较4种方法诊断膀胱癌的临床价值.结果:UBC、HA和CK20诊断膀胱癌的敏感性分别为85.9%(55/64)、89.1%(57/64)、78.1%(50/64),与脱落细胞学(40.6%)检查比较,差异有统计学意义(P<0.01);4种方法诊断膀胱癌的特异性分别为85,0%(17/20)、80.0%(16/20)、80%(16/20)和95%(19/20).各分级和分期肿瘤UBC、HA和CK20的敏感性分别高于尿脱落细胞学检查,UBC值各分级和分期比较差异无统计学意义(P>0.05).HA检测G2、G3组较G1组明显增高(P<0.01),但G2、G3组间比较差异无统计学意义(P>0.05);各分期之间比较差异无统计学意义(P>0.05).CK20检测随肿瘤的分级与分期的增高,敏感性增高(P<0.01).联合运用UBC、HA和CK20敏感性可达96.9%,特异性达100%.结论:联合UBC、HA和CK20能提高诊断膀胱癌的敏感性和特异性,初步诊断能够代替膀胱镜检查.     

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.     

The role of urinary cytology for detection of bladder cancer.

PURPOSE: The aim of the present study was to test the value of urinary cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: One thousand three hundred and eighty voided urine and bladder wash specimens of 495 patients were evaluated by urinary cytology. All patients then underwent transurethral resection of suspicious bladder areas if cystoscopy and/or preceding biopsy were positive. Statistical differences were analysed using the two-sided Fisher's exact test and Cochran's test (p<0.05). RESULTS: In 495 patients including 142 patients with bladder cancer urinary cytology revealed a sensitivity of 38.0% and a specificity of 98.3% with a positive and negative predictive value of 90.6 and 78.6, respectively. Sensitivity increased significantly with malignancy grade (p<0.05). In high grade tumours sensitivity improved from initial 52.2% up to 78.3% after the third sample. In sensitivity and specificity of voided urine and barbotage washing samples no significant difference was detected. CONCLUSIONS: Urinary cytology has its place as an additive diagnostic tool to cystoscopy. None of the currently available urinary markers can replace cystoscopy but are helpful for specific diagnostic problems.     

Soluble Fas--a promising novel urinary marker for the detection of recurrent superficial bladder cancer

BACKGROUND: The objective of this study was to test the hypothesis that elevated urinary levels of soluble Fas (sFas) would aid in the surveillance of patients with a past history of nonmuscle-invasive transitional cell carcinoma (TCC) of the urinary bladder. METHODS: sFas levels were determined in cell lysates and supernatants from 2 human bladder cancer cell lines (T24 and TCC-SUP) and in voided urine from 188 consecutive patients who were at risk for TCC recurrence, 31 patients who had noncancerous urologic conditions, and 10 healthy individuals. The authors also obtained barbotage cytology and voided nuclear matrix protein 22 (NMP22) levels. sFas was analyzed continuously and categorically on the basis of its quintile distribution. RESULTS: sFas was present in cell lysates and conditioned media from both cell lines. sFas levels were found to be higher in the TCC group (n = 122 patients) compared with the control group (P < .001). Higher levels of sFas were associated with positive cytology assay results (P < .001), higher NMP22 levels (P < .001), NMP22 levels > 10 U/mL (P < .001), and tumor stage > or = T1 (P < .001). The areas under the receiver operating characteristics (ROC) curves of sFas and NMP22 for bladder cancer detection were 0.757 (95% confidence interval, 0.694-0.819) and 0.704 (95% confidence interval, 0.637-0.772), respectively. In the > 75% sensitivity region of the ROC curves, sFas was consistently more specific than NMP22. In multivariate analyses, sFas, NMP22, and cytology all were found to be associated with the presence of bladder cancer (P values < or = .009), but only sFas and cytology were associated with tumor stage > or = T1 (P values < or = .026). CONCLUSIONS: sFas was produced and released by bladder TCC cells. Urine sFas was an independent predictor of bladder cancer recurrence and invasiveness in patients who had a past history of nonmuscle invasive bladder TCC, and it outperformed NMP22.     

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     

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.     

Assessing the clinical benefit of nuclear matrix protein 22 in the surveillance of patients with nonmuscle-invasive bladder cancer and negative cytology: a decision-curve analysis

BACKGROUND:

Several studies have demonstrated that abnormal levels of nuclear matrix protein 22 (NMP22) are associated with bladder cancer and have led to the approval of NMP22 as a urinary biomarker by the US Food and Drug Administration. Nonetheless, the clinical significance of NMP22 remains unclear. The objective of this study was to use decision analysis to determine whether NMP22 improves medical decision‐making.

METHODS:

The current study included 2222 patients who had a history of nonmuscle‐invasive bladder cancer and current negative cytology. The authors developed models to predict cancer recurrence or progression to muscle‐invasive disease using voided NMP22 levels, cystoscopy, age, and sex. Clinical net benefit was calculated by summing the benefits (true‐positives), subtracting the harms (false‐positives), and weighting these values by the threshold probability at which a patient or clinician would opt for cytoscopy.

RESULTS:

After cystoscopy, 581 patients (26%) had cancer identified. The NMP22 level was associated significantly with bladder cancer recurrence and progression (P < .001 for both). The use of NMP22 in a model with age and sex was associated with better patient outcomes than performing cystoscopy on everyone and produced threshold probabilities > 8% for recurrence and > 3% for progression. Only offering cystoscopy to those who had a risk > 15% reduced the number of cystoscopies by 229 while missing only 25 cancer recurrences per 1000 men with negative cytology. The current study was limited by its multicenter design.

CONCLUSIONS:

For clinicians who would perform a cystoscopy at a threshold of 5% for recurrence or 1% for progression, NMP22 did not aid clinical decision‐making. For less risk‐averse clinicians who would only perform a cystoscopy at a threshold probability >thinsp;8% for recurrence or > 3% for progression, NMP22 helped to indicate which patients required cystoscopy and which could be spared this procedure. Cancer 2011. © 2011 American Cancer Society.     

Role of NMP22 Bladder Check Test in Early Detection of Bladder Cancer with Recurrence

AIM: To assess clinical utility of NMP22 Bladder Chek Test and to compare it with voided urine cytologyand cystoscopy in early detection of Bladder Cancer. Material & Methods: A total of 115 patients of follow upcases of Bladder Cancer were enrolled in this study. Urine samples were assayed for the presence of NMP22using NMP22 Bladder Chek Test and Cytology was performed by a cytopathologist. The diagnosis, determinedfrom the Cystoscopic findings and biopsy findings of the suspicious lesion was considered as the gold standard.For positive biopsies, the results of the NMP22 Test and cytology were also correlated with tumour grade andstage. Results: Mean age of the patients was 57.2 years for males and 55.3 years for females. A total of 59 casesof Bladder Cancer (TCC) were diagnosed among which NMP22 test was positive in 48 cases and cytology in26 cases. The sensitivity and specificities of NMP22 Test in recurrent bladder cases was 81.3% and 92% whichwas significantly greater than that of cytology 44% and 96.1% respectively. In non-invasive lesions of BladderCancer (TCC), NMP22 Test and Cytology was positive in 71.8% and 42.8% of cases respectively. In muscleinvasivelesions, NMP22 Test was positive in 82.2% and 44.4% cases were positive for cytology. The sensitivityof the NMP22 test was 81.3%, which was significantly greater than that of cytology 44%. Conclusion: TheNMP22 Bladder Check is a new point of care diagnostic test for urinary bladder cancer. The results of our studyhave shown that the NMP22 can be used as a substitute for urine cytology as we detected high sensitivity andspecificity of NMP22 in recurrent bladder cases.