Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features

Hodges, Kurt; López-Beltrán, Antonio; Davidson, Darrell D.; Montironi, Rodolfo; Liu, Cheng

doi:10.1016/j.humpath.2009.07.002

Cited by 87 publications

(57 citation statements)

References 50 publications

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“…This immunohistochemical profile is similar to that of normal urothelium. Similar pattern is reported by Hodges et al (1) . This finding supported that flat hyperplasia does not have a premalignant potential…”

Section: Significance Of Flat Epithelial Lesions Of the ………supporting

confidence: 91%

“…It is the fourth most common cancer in men, accounting for 6.9% of all cancers, and tenth most common cancer in women, accounting for 2.6% of all cancers (1) . In Egypt, it constitutes 30.3% of all cancers (2) .…”

Section: Introductionmentioning

confidence: 99%

“…The thickness of dysplastic urothelium is usually normal, but it may be increased or decreased . Urothelial dysplasia may be primary dysplasia (rare) or secondary (more frequent) which is associated with papillary urothelial neoplasms and has higher rate of progression to carcinoma than primary dysplasia (1) . Carcinoma in situ (CIS) of the urinary bladder is defined by the replacement of part or all of the normal epithelium by cells that have microscopic and molecular features of carcinoma, yet are confined to the epithelium (8) .…”

Section: Introductionmentioning

confidence: 99%

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Significance of Flat Epithelial Lesions of the Urinary Bladder in Early Detection of Bladder Cancer: Histopathological and Immunohistochemical Study

Ramadan

Omar

Abdel-Wahed

et al. 2013

Zagazig University Medical Journal

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Background: Urothelial carcinoma of the urinary bladder is the second most common malignancy of the genitourinary system, after prostate cancer. The flat lesions are classified into flat lesions without cytological atypia (Flat hyperplasia) and flat lesions with cytological atypia; reactive atypia, atypia of unknown significance, urothelial dysplasia and urothelial carcinoma in situ). The immunohistochemical markers such as cytokeratin 20,CD 44 and Ki 67 may be useful in differentiating CIS from reactive changes in difficult biopsy cases. Aim: This study was conducted to determine the role of cytokeratin 20, CD 44 and Ki 67 in the diagnosis of dysplasia and other flat lesions of the urinary bladder. Methods: Sixty representative cases for flat urothelial lesions of urinary bladder were examined immunohistochemically using antibodies against CD44, cytokeratin 20 and Ki-67. Results: CD 44 were positive in 100%of cases of reactive urothelial atypia, but flat Hyperplasia and CIS cases were negative. However CD 44 were positive in 42.9% of atypia of unknown significance and 14.3% of Dysplasia. CK 20 were positive in (95.5%) of Dysplasia. Non of Flat Hyperplasia were positive for CK 20. However CK 20 was positive in 88.2% of CIS, 57.1 % of atypia of unknown significance and 7.1% of reactive urothelial atypia. ki 67 index were high in 82.4% of cases of CIS, non of flat hyperplasia expressed high ki 67 index. However ki 67 index were high in 57.1% of atypia of unknown significance, 52.4% of dysplasia and 14.3% of reactive urothelial atypia. Conclusion. CD 44 is the most constant marker in the reactive urothelium. CK20 is the most commonly detected marker in the dysplastic urothelium. Nevertheless, the most accurate is application of an immunohistochemical panel composed of the three antibodies (standard CD 44, CK20 and Ki-67) together with correlation with morphology. This is very useful for confirming the presence of dysplastic changes in the urothelium and differentiating reactive urothelium from dysplastic urothelium (dysplasia/CIS).

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Section: Significance Of Flat Epithelial Lesions Of the ………supporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Significance of Flat Epithelial Lesions of the Urinary Bladder in Early Detection of Bladder Cancer: Histopathological and Immunohistochemical Study

Ramadan

Omar

Abdel-Wahed

et al. 2013

Zagazig University Medical Journal

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“…Numerous promising novel biomarkers have been investigated during the last couple of years [8] , but only very few markers have been validated in prospective trials [9] . Until now, only immunohistochemical staining of p53 found its way into pathological routine diagnostics for selected cases [10,11] . Since high-grade and invasive tumors ( 6 pT1) in particular are characterized by their invasive potential and ability to metastasize, this study focuses on two key players that are well known to orchestrate tissue invasion by tissue degrading MMPs: the MMP inhibitor RECK and the activating counterpart EMMPRIN (also known as CD147).…”

Section: Introductionmentioning

confidence: 99%

Decreased RECK and Increased EMMPRIN Expression in Urothelial Carcinoma of the Bladder Are Associated with Tumor Aggressiveness

et al. 2011

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Objective: Urothelial bladder carcinomas show a divergent biological behavior, which significantly complicates risk stratification and clinical management. The MMP repressor RECK and the MMP activator EMMPRIN regulate the invasive potential by metalloproteinase-induced stromal degradation. Data on RECK in urothelial bladder cancer are lacking and information on EMMPRIN is sparse. This study aims to investigate the expression of RECK and EMMPRIN in urothelial carcinoma of the bladder and to correlate these findings with clinicopathological parameters. Methods: Our study included 127 specimens of urothelial carcinomas derived from 103 patients who underwent either TUR-B or cystectomy. Immunohistochemical expression analysis was performed for RECK, EMMPRIN, MMP-2, MMP-9 and MMP-14. Expression levels were graded for staining intensity and correlated with pT stage and WHO tumor grade. Results: Invasive (≧pT1) as well as WHO high-grade urothelial carcinomas showed a statistically significant and stepwise downregulation of RECK (p < 0.001) and concomitant upregulation of EMMPRIN (p < 0.001) compared to non-invasive and WHO low-grade tumors. No correlation was observed for the MMPs investigated. Conclusion: Decreased RECK and increased EMMPRIN expression are associated with increasing stage and grade. Both proteins may serve as molecular marker for the distinction between potentially invasive (≧pT1) and non-invasive tumors (≤pTa).

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“…The identification of TP53 mutations in slightly transformed cells (e.g. the unusual frequency of A > T transversions in p53 [−] IHC areas) supports the postulate of field cancerization consecutive to AA exposure and the hypothesis that A > T transversion in TP53 is one of the earliest events in AA-induced urothelial carcinogenesis, followed by a later occurrence and a progressive accumulation of additional genetic alterations [42].…”

Section: Discussionmentioning

confidence: 54%

TP53 mutations in p53-negative dysplastic urothelial cells from Belgian AAN patients: New evidence for aristolochic acid-induced molecular pathogenesis and carcinogenesis

Aydın

Ambroise

Cosyns

et al. 2017

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features

Cited by 87 publications

References 50 publications

Significance of Flat Epithelial Lesions of the Urinary Bladder in Early Detection of Bladder Cancer: Histopathological and Immunohistochemical Study

Significance of Flat Epithelial Lesions of the Urinary Bladder in Early Detection of Bladder Cancer: Histopathological and Immunohistochemical Study

Decreased RECK and Increased EMMPRIN Expression in Urothelial Carcinoma of the Bladder Are Associated with Tumor Aggressiveness

TP53 mutations in p53-negative dysplastic urothelial cells from Belgian AAN patients: New evidence for aristolochic acid-induced molecular pathogenesis and carcinogenesis

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