Cytokeratin 20: A New Marker for Early Detection of Bladder Cell Carcinoma

Buchumensky, V.; Klein, Ami; Zemer, Ruth; Kessler, Oded; Zimlichman, Shulamit; Nissenkorn, I

doi:10.1016/s0022-5347(01)62215-8

Cited by 59 publications

(30 citation statements)

References 15 publications

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“…Our findings concur with those of others who have demonstrated that in normal urothelium, CK20 is occasionally expressed only in terminally differentiated umbrella cells. However, we and others (20,24) observed that CK20 showed stronger and consistent IR in high-grade, less differentiated tumors. The For statistical analysis, the first two patterns and the last two were categorized as "CK20 negative" and "CK20 positive" group, respectively.…”

Section: Discussioncontrasting

confidence: 47%

“…Recently, several reports have suggested the use of a reverse transcription-polymerase chain reaction technique for the detection of CK20 expression in exfoliated urine cells as a useful, noninvasive diagnostic test for urothelial carcinoma and premalignant urothelial lesions (23,24). As indicated by Southgate et al (49), these studies were based on previous reports showing negative CK20 expression in urothelial cells grown in vitro, and it is known that urothelial cells grown in cultures fail to achieve terminal cytodifferentiation and thus do not express CK20.…”

Section: Discussionmentioning

confidence: 99%

“…A selective few include altered oncogene and tumor suppressor genes (9 -11), growth factors and growth factor receptors (12)(13)(14)(15), intermediate filament expression (8), and cell proliferation markers (8,11). Recently, CD44 and cytokeratin 20 (CK20) expression have been studied in bladder carcinoma, and the data suggest that they may be useful in the diagnosis of urothelial carcinoma on the basis of tumor immunoreactivity (IR; 16 -21) or by using reverse transcription-polymerase chain reaction in urine cytology (22)(23)(24). CK20 belongs to the epithelial subgroup of cytoskeleton-associated intermediate filaments (25) and has restricted expression in the gastrointestinal and urinary tracts, in Merkel cells, and in their respective neoplasms (25,26).…”

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confidence: 99%

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Relationship of Cytokeratin 20 and CD44 Protein Expression with WHO/ISUP Grade in pTa and pT1 Papillary Urothelial Neoplasia

et al. 2000

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The aim of this study was to assess the relationship of immunoreactivity of cytokeratin 20 (CK20) and CD44 across the spectrum of urothelial neoplasia using the WHO/ISUP consensus classification. A total of 120 papillary urothelial pTa and pT1 tumors (8 papillomas, 8 neoplasms of low malignant potential, and 42 low-grade and 62 high-grade carcinomas) were immunostained by using CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression in stage with CK20 and CD44 immunoreactivity were assessed. WHO/ISUP grade correlated with tumor stage (P < 0.005), recurrence (P ‫؍‬ 0.02), and progression in stage (P ‫؍‬ 0.031). Normal urothelium showed CK20 immunoreactivity restricted to a few umbrella cells. Expression of CD44 in normal urothelium was restricted to the basal cell layer. Loss of CD44 immunoreactivity and increasing CK20 positivity were significantly associated with increasing tumor grade and stage (P < 0.005). An inverse relationship was observed in the staining patterns of CK20 and CD44 within individual cases, as well as in the aggregate data, with 79.2% of tumors with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 and CD44 immunoreactivity are significantly related to the WHO/ISUP grade and to each other, and our data suggest their potential combined utility in predicting biologic behavior in patients with papillary urothelial pTa and pT1 neoplasms.

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Relationship of Cytokeratin 20 and CD44 Protein Expression with WHO/ISUP Grade in pTa and pT1 Papillary Urothelial Neoplasia

et al. 2000

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“…30,31 The association of cytokeratin 20 with stage and grade had previously been reported for bladder cancer both in tissue and urine specimens. [32][33][34] Comparing tumor samples by cDNA microarrays representing both early and late stage in bladder cancer progression has identified single genes that separate earlystage and invasive tumors. Two different scoring methods, t-test and single logistic regression analysis, have provided more than 200 genes that segregate earlystage and invasive groups of bladder tumors under cDNA analysis.…”

Section: Discussionmentioning

confidence: 99%

Gene Discovery in Bladder Cancer Progression using cDNA Microarrays

Sänchez‐Carbayo

Socci

Lozano

et al. 2003

The American Journal of Pathology

169

130

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To identify gene expression changes along progression of bladder cancer, we compared the expression profiles of early-stage and advanced bladder tumors using cDNA microarrays containing 17,842 known genes and expressed sequence tags. The application of bootstrapping techniques to hierarchical clustering segregated early-stage and invasive transitional carcinomas into two main clusters. Multidimensional analysis confirmed these clusters and more importantly, it separated carcinoma in situ from papillary superficial lesions and subgroups within early-stage and invasive tumors displaying different overall survival. Additionally, it recognized early-stage tumors showing gene profiles similar to invasive disease. Different techniques including standard t-test, singlegene logistic regression, and support vector machine algorithms were applied to identify relevant genes involved in bladder cancer progression. Cytokeratin 20, neuropilin-2, p21, and p33ING1 were selected among the top ranked molecular targets differentially expressed and validated by immunohistochemistry using tissue microarrays (n ‫؍‬ 173). Their expression patterns were significantly associated with pathological stage, tumor grade, and altered retinoblastoma (RB) expression. Moreover, p33ING1 expression levels were significantly associated with overall survival. Analysis of the annotation of the most significant genes revealed the relevance of critical genes and pathways during bladder cancer progression, including the overexpression of oncogenic genes such as Transitional cell carcinomas (TCCs) of the bladder define a group of histologically and genetically diverse cancers that account for ϳ4% of all adult malignancies with an annual incidence of ϳ53,200 cases in the United States. Early-stage TCC has been classified into two groups with distinct clinical behavior and different molecular profiles. Superficial low-grade tumors (Ta) are always papillary and may recur but rarely progress, whereas high-grade tumors can be either papillary or flat lesions (Tis) and often progress to invasive disease.2 Clinically, patients diagnosed with localized stage have a 5-year relative survival rate of 93%. However, patients presenting with regional and distant stage have 5-year relative survival rates of 49% and 6%, respectively.1 Among the molecular events that characterize superficial papillary noninvasive bladder tumors are deletions affecting the long arm of chromosome 9, and activation of certain oncogenes, such as H-RAS, alterations identified only in a subset of invasive bladder neoplasms.2 Deletions of 13q at the RB locus and 17p at the TP53 locus, as well as 18q (DCC locus) and 5q (APC locus) losses have been reported in invasive bladder transitional carcinomas, but are absent in papillary noninvasive tumors.2,3 A remaining challenge in bladder cancer is to define targets characteristic of aggressive early-stage tumors before they recur or progress into invasive disease. The present study was designed to identify critical molecular targets altered along the...

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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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Cytokeratin 20: A New Marker for Early Detection of Bladder Cell Carcinoma

Cited by 59 publications

References 15 publications

Relationship of Cytokeratin 20 and CD44 Protein Expression with WHO/ISUP Grade in pTa and pT1 Papillary Urothelial Neoplasia

Relationship of Cytokeratin 20 and CD44 Protein Expression with WHO/ISUP Grade in pTa and pT1 Papillary Urothelial Neoplasia

Gene Discovery in Bladder Cancer Progression using cDNA Microarrays

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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