Molecular pathology of non-invasive urothelial carcinomas (part I)

Helpap, B.; Schmitz‐Dräger, Bernd J.; Hamilton, Peter; Muzzonigro, Giovanni; Galosi, Andrea Benedetto; Kurth, K. H.; Lubaroff, David M.; Waters, David J.; Droller, Michael J.

doi:10.1007/s00428-002-0748-0

Cited by 37 publications

(17 citation statements)

References 48 publications

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“…An important goal of array investigations of UC is the development of biomarkers for prognostic purposes. This aim has so also been pursued by investigations focused on individual genes, the most prominent one being TP53 32, 33, 34. The TP53 tumor suppressor gene harbors missense mutations in up to 50% of bladder cancers.…”

Section: Tp53 As a Biomarker In Ucmentioning

confidence: 99%

“…Moreover, LOH at 17p is preferentially found in advanced cases. Evidently, TP53 mutations are associated with an increased risk of progression in bladder cancer 3, 4, 32, 33, 34. The moot point is whether detection of TP53 mutations can predict the natural course of the disease or responses to therapy better than histopathological parameters.…”

Section: Tp53 As a Biomarker In Ucmentioning

confidence: 99%

“…The correlation between mutations and nuclear accumulation of TP53 is very good in bladder cancer, but not perfect. In addition, TP53 immunohistochemistry poses its own vagaries, although standardized techniques have meanwhile been developed 32, 33, 34…”

Section: Tp53 As a Biomarker In Ucmentioning

confidence: 99%

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Understanding urothelial carcinoma through cancer pathways

Schulz

2006

Intl Journal of Cancer

100

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Urothelial carcinoma (UC), the common histological subtype of bladder cancer, presents as a papillary tumor or as an invasive, often lethal form. To study UC molecular biology, candidate gene and genome-wide approaches have been followed. Here, it is argued that a Ôcancer pathwayÕ perspective is useful to integrate findings from both approaches. According to this view, papillary cancers typically exhibit activation of the MAPK pathway, as a consequence of oncogenic mutations in FGFR3 or HRAS, with increased Cyclin D1 expression. In contrast, invasive UC are characterized by severe disturbances in proximate cell cycle regulators, e.g. RB1 and CDKN2A/p16 INK4A , which decrease dependency on mitogenic signaling. In addition, these disturbances permit, promote and are in turn exacerbated by chromosomal instability, which is further enhanced by loss of TP53 function. In another vicious cycle, defective cell cycle regulation interacts with DNA methylation alterations. The transition toward invasive UC may require concomitant and interacting defects in cell cycle regulation and the control of genomic stability. Intriguingly, neither canonical WNT/b-Catenin nor hedgehog signaling appear to play major roles in UC. This may reflect its origin from more differentiated urothelial cells possessing a high regenerative potential rather than a stem cell population. ' 2006 Wiley-Liss, Inc.

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Section: Tp53 As a Biomarker In Ucmentioning

confidence: 99%

Section: Tp53 As a Biomarker In Ucmentioning

confidence: 99%

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Understanding urothelial carcinoma through cancer pathways

Schulz

2006

Intl Journal of Cancer

100

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“…3,4 On the other hand, papillary bladder cancer comprises different types of tumors with varying biologic potential and distinct pathways of development. 5,6 The 5-year survival rate is approximately 94% in patients with localized bladder cancer but decreases to 6% in those developing metastatic disease. 7 Early detection of primary and recurrent, potentially aggressive bladder cancer is thus an important determinant of treatment success.…”

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confidence: 99%

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Weikert

Krause

Wolff

et al. 2005

Intl Journal of Cancer

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The aim of our study was to prospectively evaluate the potential diagnostic value and clinical applicability of quantitative analysis of telomerase subunits gene expression in urine for noninvasive detection of bladder cancer. Expression levels of human telomerase reverse transcriptase (hTERT) and human telomerase RNA (hTR) were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in urine samples from 163 subjects with bladder cancer and 237 controls (163 individuals with benign genitourinary diseases; 74 healthy subjects). The sensitivity, specificity and optimal cutoffs were determined and compared to the corresponding values obtained by voided urine cytology. Quantitative urinary hTR analysis detects bladder cancer with an overall sensitivity of 77.0%, whereas hTERT analysis reached a sensitivity of 55.2%. The majority of undetected tumors were small, lowgrade pTa lesions. Both hTR and hTERT proved to be significantly more sensitive than cytology (34.5%; p < 0.001). Specificities for hTR, hTERT and cytology were 72.1%, 85.0% and 92.7%, respectively, in the total study population and 96.9%, 89.2% and 100%, respectively, in healthy subjects. Higher diagnostic accuracy was achieved by hTR than by hTERT analysis (p < 0.05). The specificity of hTR increased to 85.0% in the total population if urinary leukocyte contamination was excluded. These data suggest that quantitative hTR analysis is the most accurate telomerase-based test for bladder cancer detection and has the potential to replace cytology as a noninvasive biomarker for disease diagnosis and follow-up. ' 2005 Wiley-Liss, Inc.

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“…In the present study 84 % cases could achieve a histological diagnosis on basis of histomorphology alone, and in 16 % cases IHC was required for final diagnosis, mainly to differentiate between Papillomas / Non-invasive PUNLMP/Non-invasive PUCLG. Many studies done by Alrashidy et al [15] Eble et al [8] Mallofre et al [13] Helpap et al [16] have also reported that distinguishing urothelial papillomas/ PUNLMP and papillary carcinomas especially non-invasive low grade one is sometimes difficult on the basis of histomorphological features alone and IHC markers may be used as an adjuvant to histology to arrive at a final diagnosis in these cases. IHC markers (CK20, p53 and Ki67) were applied on cases with differential diagnosis of UP / PUNLMP, IP/ PUCLG, UP/ PUCLG and PUNLMP/ PUCLG.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of CK20, p53 and KI67 to differentiate between Papillomas/Non-Invasive papillary urothelial Neoplasm of low malignant potential/non-invasive papillary urothelial carcinoma, low grade

Gajjar¹,

Faujdar²,

Jain³

et al. 2019

Int. J. Clin. Diagn. Pathol.

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Background: Urinary Bladder cancer is the 7th most common cancer worldwide, with an estimated 260,000 new cases occurring each year in men and 76,000 in women. It is estimated that approximately 70-80% of patients with newly diagnosed bladder cancer present with non-invasive or early invasive. The problem arise mostly in distinguishing urothelial papilloma from non-invasive PUNLMP & papillary carcinoma especially low grade noninvasive ones. It is very important to distinguish these entities to design the therapeutic and monitoring strategies for these patients and it is difficult on the basis of histological features alone. Aim & Objectives: To study histomorphological spectrum of urothelial tumors according to WHO/ISUP consensus (2004) and to study pattern of expression of CK20, p53 LI & Ki67 LI to differentiate between Papillomas/PUNLMP/PUCLG. Material & Method: In this study 300 consecutive cases were taken from March 2016 to May 2017. Cases were histomorphologically classified according to WHO/ISUP (2004) classification & investigated the role of IHC panel of CK20, p53 & Ki67 to evaluate their utility for the diagnosis & to differentiate between Papilloma/PUNLMP/PUCLG. Results: Out of 300 cases, 48 cases were required IHC (CK20, p53, Ki67) for final diagnosis. Out of 48 cases, 16 were diagnosed as PUCLG, 10 were diagnosed as PUNLMP. Urothelial papilloma and Inverted urothelial papilloma were diagnosed in 13 and 9 cases respectively. Conclusion: The WHO/ISUP (2004) classification for bladder tumor enables to diagnose urothelial tumors into clinically and prognostically relevant entities. IHC panel of CK20, p53 & Ki67 may be a useful diagnostic marker in Papillary urothelial neoplasms, especially Non-invasive urothelial neoplasias at the lower end of the spectrum & help to differentiate papilloma/PUNLMP/PUCLG with borderline histological features.

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Molecular pathology of non-invasive urothelial carcinomas (part I)

Cited by 37 publications

References 48 publications

Understanding urothelial carcinoma through cancer pathways

Understanding urothelial carcinoma through cancer pathways

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Diagnostic utility of CK20, p53 and KI67 to differentiate between Papillomas/Non-Invasive papillary urothelial Neoplasm of low malignant potential/non-invasive papillary urothelial carcinoma, low grade

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