Urinary Cytokeratin 20 as a Marker for Transitional Cell Carcinoma

Rotem, D.; Cassel, Aliza; Lindenfeld, Noemi; Mecz, Yoel; Sova, Yanina; Resnick, Murray B.; Stein, Avi

doi:10.1159/000020199

Cited by 41 publications

(30 citation statements)

References 11 publications

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“…[22][23][24] CK-20 is differentially expressed in bladder carcinoma tissue and in some umbrella cells of normal urothelial cells. 10,25 The application by Klein, et al 26 and Rotem, et al 27 of RT-PCR for detection of CK-20 RNA in cells isolated from urine has been supported by the current study findings, summarized in Figure 2, which show the appearance of the specific PCR product 370 bp band in the urine cells of patients with bladder carcinoma. Similar to previous reports, 26 -28 CK-20 demonstrated very high Regarding grading, most false-negative results were in Grade 1 (42.3%), implying a significant correlation between CK-20 test and grading.…”

Section: Discussionsupporting

confidence: 79%

“…Similar to previous reports, 26 -28 CK-20 demonstrated very high Regarding grading, most false-negative results were in Grade 1 (42.3%), implying a significant correlation between CK-20 test and grading. 27 With respect to staging, despite the significant correlation between CK-20 positivity and tumor staging, lower sensitivity in Stage 0 (41.2%) and Stage 1 (71.3%), limits the usefulness of CK-20 as an early diagnostic test for bladder carcinoma. Klein, et al 26 reported higher sensitivity (84% of Ta compared with 75% in the current study).…”

Section: Discussionmentioning

confidence: 99%

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Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs

Eissa

Kassim

Labib

et al. 2005

Cancer

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BACKGROUNDA new, sensitive, noninvasive method for the detection of urothelial carcinomas of the urinary bladder would open new possibilities in both the diagnosis and followup of patients.METHODSThis study included 228 patients diagnosed with bladder carcinoma, 68 patients with benign bladder lesions, and 44 healthy persons served as the control group. All were subjected to: serologic schistosomiasis antibody assay in serum, urine cytology, estimation of urine hyaluronic acid (HA) by enzyme‐linked immunosorbent assay, and detection of CK‐20 and hyaluronidase (HAase) by reverse transcription polymerase chain reaction (RT‐PCR) in urothelial cells from voided urine.RESULTSHA mean rank was higher in benign and malignant groups than in the healthy group (P < 0.0001) and was significantly related to tumor grade (P = 0.021). HA best‐cutoff, determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups, was 58.5 units/mg protein at 85.8% sensitivity and 60.7% specificity. HAase RNA showed superior sensitivity (90.8%) over cytology (68.9%) and CK‐20 (78.1%) with specificity of 93.4%, 98.1% and 80.2%, respectively. The sensitivity reached 94.7% at a specificity of 91.5% when combined with CK‐20. All 4 of the investigated markers were related to grade at P <0.05. Whereas only HAase and CK‐20 were significantly related to stage (P < 0.05). As to schistosomiasis, only HAase RNA positivity was significantly associated (P = 0.038).CONCLUSIONSHAase RNA is a promising noninvasive test with high sensitivity and specificity in bladder carcinoma detection. Cancer 2005. © 2005 American Cancer Society.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs

Eissa

Kassim

Labib

et al. 2005

Cancer

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“…A diagnostic assay for keratin 20 based on RT-PCR of urine samples has been reported, confirming the potential of this technical approach for diagnosis (Rotem et al, 2000). Genes connected to other epithelial cells' functions (e.g.…”

Section: Molecular Analysis Of Tccmentioning

confidence: 67%

“…Proteins that are secreted, like HAI-2 and syndecan-1 (both of which are overexpressed in several cancers; Bayer-Garner et al, 2000;Dobra et al, 2000;Itoh et al, 2000;Kataoka et al, 2000), are suitable for the development of a noninvasive urine-based diagnostic test for TCC. Alternatively, an RT-PCR-based test on urine samples may be developed for genes coding for intracellular proteins, since the transitional epithelium cells are exfoliated in the urine in both normal and disease conditions (Rotem et al, 2000). Many of the genes that were shown to be overexpressed in noninvasive TCC compared to normal urothelium are characteristic of dedifferentiated epithelial cells, some of which (keratins 7, 8, 18 and 19) have already been Figure 4 Genes that obtained the highest positive factor scores within the four identified PCA factors.…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of transitional cell carcinoma using cDNA microarray

et al. 2003

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“…Multimarkers to enhance diagnostic accuracy The 2 biomarkers CK20 and CD44v6 used in combination in our study to mark UETCs achieved an accurate diagnosis of bladder cancer (with a validated AUC of 0.84, sensitivity of 89.8% and specificity of 71.5%), because both of them have been separately employed to mark and identify bladder cancer in tumor tissues (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45).…”

Section: Advantages Of a Chip-based Microfluidic Approachmentioning

confidence: 95%

Detection of Urothelial Bladder Carcinoma via Microfluidic Immunoassay and Single-Cell DNA Copy-Number Alteration Analysis of Captured Urinary-Exfoliated Tumor Cells

Chen

et al. 2018

Cancer Research

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The increasing incidence of bladder cancer and its high rate of recurrence over a 5-year period necessitate the need for diagnosis and surveillance amelioration. Cystoscopy and urinary cytology are the current tools, and molecular techniques such as BTA stat, NMP22, survivin mRNA, and urovysion FISH have attracted attention; however, they suffer from insufficient sensitivity or specificity. We developed a novel microfluidic approach for harvesting intact urinary-exfoliated tumor cells (UETC), either individually or in clusters, in a clean and segregated environment, which is crucial to minimize crosscontamination and misreads. To reliably and accurately identify UETC, our quantitative immunoassay involved concurrent use of two oncoproteins CK20 and CD44v6 antigen. CK20 is an intermediate filament protein overexpressed in urothelial tumors, and CD44v6 is a membrane adhesion molecule closely associated with cell invasion, tumor progression, and metastatic spread. Single-cell whole-genome sequencing on 12 captured UETCs and copy number alteration analysis showed that 11/12 (91.7%) of the immunofluorescence-identified UETCs possessed genomic instability. A total of 79 patients with bladder cancer and 43 age-matched normal controls (NC) were enrolled in the study. We detected considerably higher UETC counts in patients with bladder cancer versus the NC group [53.3 (10.7-1001.9) vs. 0.0 (0-3.0) UETCs/10 mL; P < 0.0001]. For bladder cancer detection, a stratified 10-fold cross-validation of training data reveals an overall predictive accuracy of 0.84 [95% confidence interval (CI), 0.76-0.93] with an 89.8% (95% CI, 71.5%-86.4%) for sensitivity and 71.5% (95% CI, 59.7%-83.3%) for specificity. Overall, the microfluidic immunoassay demonstrates increased sensitivity and specificity compared with other techniques for the detection of bladder cancer.Significance: A unique and promising diagnostic assay for bladder cancer is proposed with potential clinical utility as a complement for cytology. Cancer Res; 78(14); 4073-85. Ó2018 AACR.

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Urinary Cytokeratin 20 as a Marker for Transitional Cell Carcinoma

Cited by 41 publications

References 11 publications

Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs

Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs

Molecular analysis of transitional cell carcinoma using cDNA microarray

Detection of Urothelial Bladder Carcinoma via Microfluidic Immunoassay and Single-Cell DNA Copy-Number Alteration Analysis of Captured Urinary-Exfoliated Tumor Cells

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