Urinary concentrations of the soluble adhesion molecule E-cadherin and total protein in patients with bladder cancer

Protheroe, Andrew; Banks, Rosamonde E.; Mzimba, M; Porter, W H; Southgate, Jennifer; Singh, Priya; Bosomworth, M.; Harnden, Patricia; Smith, Philip H.; Whelan, Peter; Selby, Peter J.

doi:10.1038/sj.bjc.6690351

Cited by 31 publications

(24 citation statements)

References 42 publications

(48 reference statements)

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“…The soluble cleaved form of E-cadherin has been observed in serum under non-pathological conditions, but increased levels of the soluble form have been detected in patient peripheral blood samples 24,54 and urine samples 55 in a variety of diseases. 21 It has been suggested that the 80-kDa soluble fragment may serve as a useful biomarker of disease progression for a number of cancers, including prostate, 23 gastric, 24 hepatocellular 24 and bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

“…21 It has been suggested that the 80-kDa soluble fragment may serve as a useful biomarker of disease progression for a number of cancers, including prostate, 23 gastric, 24 hepatocellular 24 and bladder cancer. 55 There has also been a correlation between tumor stage, histological grade and elevated levels of soluble E-cadherin, likely because the detection of soluble E-cadherin has been associated with increased invasiveness. 23,56,57 Although reasonable, it is currently unknown whether the detection of the C-terminal fragment of E-cadherin in the nucleus of CC-RCC correlates with increased serum level of soluble N-terminal E-cadherin fragment.…”

Section: Discussionmentioning

confidence: 99%

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Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma

Gervais

Henry

Saravanan

et al. 2007

Laboratory Investigation

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The loss of functional von Hippel-Lindau (VHL) tumor suppressor gene is associated with the development of clear-cell renal cell carcinoma (CC-RCC). Recently, VHL was shown to promote the transcription of E-cadherin, an adhesion molecule whose expression is inversely correlated with the aggressive phenotype of numerous epithelial cancers. Here, we performed immunohistochemistry on CC-RCC tissue microarrays to determine the prognostic value of E-cadherin and VHL with respect to Fuhrman grade and clinical prognosis. Low Fuhrman grade and good prognosis associated with positive VHL and E-cadherin immunoreactivity, whereas poor prognosis and high-grade tumors associated with a lack of E-cadherin and lower frequency of VHL staining. A significant portion of CC-RCC with positive VHL immunostaining correlated with nuclear localization of C-terminally cleaved E-cadherin. DNA sequencing revealed in a majority of nuclear E-cadherin-positive CC-RCC, subtle point mutations, deletions and insertions in VHL. Furthermore, nuclear E-cadherin was not observed in chromophobe or papillary RCC, as well as matched normal kidney tissue. In addition, nuclear E-cadherin localization was recapitulated in CC-RCC xenografts devoid of functional VHL or reconstituted with synthetic mutant VHL grown in SCID mice. These findings provide the first evidence of aberrant nuclear localization of E-cadherin in CC-RCC harboring VHL mutations, and suggest potential prognostic value of VHL and E-cadherin in CC-RCC. [4][5][6][7] Currently, a prediction of patient survival is based on traditional clinical parameters, including tumor size and Fuhrman nuclear grade. 8 However, the emerging understanding of the molecular pathways implicated in CC-RCC genesis and progression is providing previously unappreciated markers, which may serve as additional or better prognostic indicators of CC-RCC.The principal cause of sporadic CC-RCC and familial von Hippel-Lindau (VHL) disease-associated CC-RCC is the inactivating mutations of VHL. Although VHL patients also develop tumors in other organs including the central nervous system, retina and the adrenal gland, CC-RCC remains to be the leading cause of morbidity and death for VHL patients. 9 The most well-established function of VHL is its role in the oxygen-dependent negative regulation of hypoxia-inducible factor (HIF). VHL is a substrate-conferring component of an E3 ubiquitin ligase ECV (elongins/Cul2/VHL) that polyubiquitylates the catalytic a-subunit of HIF that has undergone hydroxylation on conserved prolyl residues within the oxygen-dependent degradation (ODD) domain. Prolyl hydroxylation is mediated by a class of prolyl hydroxylases (PHD1-3) in an oxygen-dependent manner. Thus, under hypoxia or in the absence of a functional VHL, HIFa becomes stabilized and binds to its common and constitutively expressed b-subunit, forming an active HIF transcription factor capable of transactivating numerous hypoxia-inducible genes such as vascular endothelial growth factor (VEGF),

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma

Gervais

Henry

Saravanan

et al. 2007

Laboratory Investigation

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“…This may be considered as a reflection of increased protein excretion in urine of bladder cancer patients detected herein and reported earlier 18,35 and attributed either to leakage of serum proteins from the tumor neovasculature, or to increased turnover of bladder cancer cells. 18 If this holds true however, the specificity of the assay may be affected by the presence of renal disease, and this will have to be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…The bladder tumor antigen, 4 the bladder tumor antigen stat, 5 the fibrinogen/fibrin degradation products, 6 and the nuclear matrix protein-22 tests, 3,7 have been approved by the Food and Drug Administration to be used in conjunction with cystoscopy. Additional molecular assays currently being evaluated for their diagnostic/prognostic utility 2,3,8,9 are the Telomerase, 10 Immunocyt, 11 and hyaluronic acid/hyaluronidase 12,13 tests, microsatellite analysis, 14 as well as assays detecting blood group antigens, 15 carcinoembryonic antigen, 16 p53 and retinoblastoma proteins, 3 E cadherin, 17,18 and various growth factors. 9 Because of the molecular heterogeneity of these tumors, it is likely that there will be no single molecular assay that will replace cystoscopy.…”

mentioning

confidence: 99%

Development of a Novel Proteomic Approach for the Detection of Transitional Cell Carcinoma of the Bladder in Urine

Vlahou

Schellhammer

Mendrinos

et al. 2001

The American Journal of Pathology

383

241

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Development of noninvasive methods for the diagnosis of transitional cell carcinoma (TCC) of the bladder remains a challenge. A ProteinChip technology (sur-faceBladder cancer is the second most common genitourinary malignancy accounting for ϳ5% of all newly diagnosed cancers in the United States. 1 More than 90% are of the transitional cell carcinoma (TCC) histology. 2 At present, the most reliable way of diagnosis and surveillance of TCC is by cystoscopic examination and bladder biopsy for histological confirmation. The invasive and labor-intensive nature of this procedure presents a challenge to develop better, less costly, and noninvasive diagnostic tools. Urine cytology has for many years been the gold standard of the noninvasive approaches. It has high specificity and provides the advantage over biopsy of screening the entire urothelium. 2,3 However, its high false-negative rate, particularly for low-grade tumors, has limited its use as an adjunct to cystoscopy.Many noninvasive molecular diagnostic tests have been developed based on an ever-increasing knowledge about the molecular alterations associated with bladder cancer pathogenesis. The bladder tumor antigen, 4 the bladder tumor antigen stat, 5 the fibrinogen/fibrin degradation products, 6 and the nuclear matrix protein-22 tests, 3,7 have been approved by the Food and Drug Administration to be used in conjunction with cystoscopy. Additional molecular assays currently being evaluated for their diagnostic/prognostic utility 2,3,8,9 are the Telomerase, 10

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“…In a recent study, an 80 kDa fragment of full-length e-cadherin has been described as almost exclusively being observed in the neoplastic aspect of prostate cancer tissue (Kuefer et al, 2003). This soluble fragment has also been reported as being measurable in the serum of patients suffering from different types of adenocarcinoma (Katayama et al, 1994a;Banks et al, 1995;Gofuku et al, 1998;Velikova et al, 1998;Protheroe et al, 1999;Chan et al, 2003). In the current study, we report the accumulation of this 80 kDa fragment of e-cadherin in the serum of patients affected by prostate cancer.…”

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confidence: 99%

Assessment of a fragment of e-cadherin as a serum biomarker with predictive value for prostate cancer

et al. 2005

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In prostate cancer, biomarkers may provide additional value above standard clinical and pathology parameters to predict outcome after specific therapy. The purpose of this study is to evaluate an 80 kDa fragment of the cell adhesion molecule e-cadherin as a serum biomarker. A broad spectrum of prostate cancer serum samples, representing different stages of prostate cancer disease, including benign prostatic hyperplasia (BPH), localised (Loc PCA) and metastatic prostate cancer (Met PCA), was examined for the cleaved product. There is a significant difference in the expression level of the 80 kDa fragment in the serum of healthy individuals vs patients with BPH and between BPH vs Loc PCA and Met PCA (Po0.001). Highest expression levels are observed in advanced metastatic disease. In the cohort of Loc PCA cases, there was no association between the 80 kDa serum concentration and clinical parameters. Interestingly, patients with an 80 kDa level of 47.9 mg l À1 at the time of diagnosis have a 55-fold higher risk of biochemical failure after surgery compared to those with lower levels. This is the first report of the application of an 80 kDa fragment of e-cadherin as a serum biomarker in a broad spectrum of prostate cancer cases. At an optimised cutoff, high expression at the time of diagnosis is associated with a significantly increased risk of biochemical failure, potentially supporting its use for a tailored follow-up protocol for those patients.

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Urinary concentrations of the soluble adhesion molecule E-cadherin and total protein in patients with bladder cancer

Cited by 31 publications

References 42 publications

Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma

Nuclear E-cadherin and VHL immunoreactivity are prognostic indicators of clear-cell renal cell carcinoma

Development of a Novel Proteomic Approach for the Detection of Transitional Cell Carcinoma of the Bladder in Urine

Assessment of a fragment of e-cadherin as a serum biomarker with predictive value for prostate cancer

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