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Urothelial Carcinoma (urothelial + carcinoma)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Urology	45%
Pathology	25%
Oncology & Radiotherapy	20%
2 Other Subdomains	10%

Kinds of Urothelial Carcinoma

high-grade urothelial carcinoma

Selected Abstracts

High incidence of and risk factors for metachronous bilateral upper tract urothelial carcinoma in Taiwan

INTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2006
PO-CHIEN HUANG
Aim:, Urothelial carcinoma (UC) can occur multifocally in the whole urothelium. A higher rate of bilateral metachronous upper tract (UT) UC was noted in Taiwan. The incidence and risk factors were largely unknown and hence were explored in the study. Methods:, From January 1977 through June 2003, 462 patients with unilateral UT-UC were studied retrospectively. The cumulative incidence of contralateral recurrence was analysed with the Kaplan,Meier analysis. Potential risk factors for contralateral recurrence including age, smoking, bladder cancer, renal function, diagnostic year etc. were evaluated with the log,rank test. Independent risk factors were identified by using the Cox regression analysis. Results:, The median follow-up time was 34 months (6,337). Among the 462 patients, 52 (11.3%) developed metachronous contralateral UC. The 2, 5, and 10-year contralateral disease-free survivals were 93.5%, 84.0%, and 75.7%, respectively. The median time to contralateral recurrence was 31.0 months. With the univariate analysis, only poor renal function (serum creatinine < or ,2.0 mg/dL, P < 0.001) and late diagnostic year (before or after 1990, P < 0.001) were risk factors for contralateral recurrence. In the multivariate analysis, poor renal function (hazard ratio: 2.98; 95% confidence interval: 1.67,5.33; P < 0.001) and late diagnostic year (hazard ratio: 4.27; 95% confidence interval: 1.71,10.65; P = 0.002) remained independent risk factors. Conclusions:, The incidence of metachronous UT-UC is high in Taiwan. Patients who had either chronic renal insufficiency or a disease diagnosed after 1990 had a higher risk of contralateral recurrence. [source]

Urine cytological findings of plasmacytoid urothelial carcinoma of urinary bladder: report of two cases

CYTOPATHOLOGY, Issue 4 2009
T. Sakuma
First page of article [source]

Fine needle aspiration of renal cortical lesions in adults

DIAGNOSTIC CYTOPATHOLOGY, Issue 10 2010
Adebowale J. Adeniran M.D.
Abstract The role of fine needle aspiration (FNA) biopsy of renal cortical lesions was controversial in the past because the result of the FNA did not affect clinical management. All renal cortical lesions, except metastasis, were subject to surgical resection. However, with the advances in neoadjuvant targeted therapies, knowledge of the renal cortical tumor histological subtype is critical for tailoring clinical trials and follow-up strategies. At present, there are clinical trials involving the use of novel kinase inhibitors for conventional (clear cell) and papillary renal cell carcinoma. We studied 143 consecutive cases of renal cortical lesions, evaluated after radical or partial nephrectomies over a 2-year period. An air-dried smear and a Thinprep® slide were prepared in all cases. The slides were Diff-Quick and Papanicolaou stained, respectively. The cytology specimens were reviewed and the results were then compared with the histologic diagnosis. Cytology was highly accurate to diagnose conventional RCC, while the accuracy for papillary RCC, chromophobe RCC, and papillary urothelial carcinoma was much lower. Our results indicate that ancillary studies might have an important role in the subclassification of renal cortical neoplasms for targeted treatment. Diagn. Cytopathol. 2010;38:710,715. © 2009 Wiley-Liss, Inc. [source]

Cytomorphology of lymphoepithelioma-like carcinoma of the urinary bladder: Report of two cases

DIAGNOSTIC CYTOPATHOLOGY, Issue 8 2008
Guoping Cai M.D.
Abstract Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is a rare variant of high-grade urothelial carcinoma. Here, we report urine cytologic findings in two cases of this rare entity, the diagnosis of which was confirmed by histopathological examination of the resected tumors. The cytomorphologic features included large tumor cells with high nuclear to cytoplasmic ratios, vesicular chromatin, and prominent nucleoli, presented as single cells or intermixed with inflammatory cells. The differential diagnosis included otherwise typical high-grade urothelial carcinoma, reactive urothelial cells and rarely large cell lymphoma. The rarity of the tumor cells may impose a diagnostic challenge in urine specimen. Diagn. Cytopathol. 2008; 36: 600,603. © 2008 Wiley-Liss, Inc. [source]

Exfoliative sputum cytology of cancers metastatic to the lung,

DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005
Tehmina Z. Ali M.D.
Abstract Although largely replaced by fine-needle aspiration (FNA) and bronchoscopy, cytological examination of sputum for exfoliated malignant cells still is considered a valuable initial diagnostic test in patients presenting with a lung mass. Thirty-five cases of secondary/metastatic tumors involving the lung and diagnosed on sputum were retrospectively reviewed from our cytopathology files for a period of 22 yr (1980,2001). Clinical history and the relevant histopathological material were examined and correlated with the cytological findings. In all cases, a history of malignancy was known. Cytological diagnoses included colonic adenocarcinoma (7 cases); non-Hodgkin's lymphoma (NHL; 5 cases); malignant melanoma (MM; 5 cases); breast carcinoma (5 cases); Hodgkin's lymphoma (HL; 3 cases); pancreatic adenocarcinoma (2 cases); prostatic adenocarcinoma (2 cases); and 1 case each of urothelial carcinoma, endometrial carcinoma, renal cell carcinoma, hepatic small-cell carcinoma, squamous-cell carcinoma (cervix), and leiomyosarcoma (LMS). Cellular preservation was optimal in all cases. The smear background was relatively clean in 25 (71%) cases and predominantly inflamed and/or necrotic in 10 (29%) cases. In non-lymphoid tumors (27 cases), isolated single malignant cells were seen in 7 (26%) cases (all cases of MM and prostatic adenocarcinoma), whereas 20 (74%) cases displayed fragments with intact tumor architecture. Overall, only 10/35 (29%) cases showed noticeable tumor-cell necrosis. In one case (LMS), cell block sections were used for immunoperoxidase (IPOX) studies with positive staining for desmin and actin. Exfoliation of cancer cells in sputum from secondary tumors in the lung is a rare phenomenon in current-day practice, with metastatic colonic adenocarcinoma seen most commonly. Intact tumor architecture was observed in exfoliated cells in 75% of the cases. Diagn. Cytopathol. 2005;33:147,151. © 2005 Wiley-Liss, Inc. [source]

Urinary bladder biopsy with denuded mucosa: Denuding cystitis,Cytopathologic correlates

DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2004
Anil V. Parwani M.D., Ph.D.
Abstract Denuding cystitis is often encountered in tissue biopsies of bladder mucosa performed by either cold-cup forceps or wire loop electrocautery to evaluate hematuria or to rule out recurrent urothelial carcinoma. Lack of urothelium in these biopsies is often a frustrating experience, leading to a nonspecific interpretation. In this study, 151 cases of denuding cystitis were retrieved from the surgical pathology files of The Johns Hopkins Hospital over a 4-year period (1996,1999). Patients under the age of 40 years and outside consultation material were excluded. Of the 151 cases of denuding cystitis, 48 patients were identified who had concurrent urinary cytologic studies. Of these patients, 35 were male (73%) and 13 were female (27%). Patient ages ranged from 43 to 85 years (mean, 67). Twenty-six of these 48 patients (54%) had at least one concurrently positive urinary cytology, which was histologically confirmed. All except three cases were high-grade urothelial carcinoma with the following histologic subtypes: flat carcinoma in situ (n = 11), noninvasive papillary (n = 9), and invasive urothelial carcinoma (n = 3). We conclude that urinary cytology is a sensitive modality that detects exfoliated carcinoma cells in patients with a histologic diagnosis of denuding cystitis. An inconclusive diagnosis of denuding cystitis on tissue might be related to biopsy method and technique, small sample size, or biopsy of cystoscopically abnormal urothelium that is denuded. A cytologic diagnosis of high-grade urothelial carcinoma in these cases leads to a timely clinical intervention for optimal patient management. Diagn. Cytopathol. 2004;30:297,300. © 2004 Wiley-Liss, Inc. [source]

Low-grade urothelial carcinoma: Reappraisal of the cytologic criteria on ThinPrep®

DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2003
Ph.D., Wei Xin M.D.
Abstract The diagnostic criteria for low-grade urothelial lesions that have been described in the past were based on urinary specimens prepared by the cytospin method. Recognizing the recent popularity of the ThinPrep® methodology and the cytologic alterations it introduces to the cellular features, we sought to evaluate the reproducibility of these criteria in ThinPrep urinary samples. One hundred twenty-six ThinPrep urinary specimens with a tissue diagnosis of low-grade urothelial carcinoma (LGUC) and 45 negative controls were evaluated. Three pathologists blindly reviewed the slides separately and the consensus on each feature was used in the study. Logistic regression analysis was used to determine which criteria in combination were most predictive of low-grade urothelial carcinoma. All specimens were evaluated for the following 18 features: nucleus/cytoplasm ratio, irregular nuclear border, cytoplasm homogeneity, cell clusters, high cellularity, prominent nucleoli, granular nuclear chromatin, hyperchromasia, acute inflammation, vesicular chromatin, nuclear molding, nuclear eccentricity, elongated nuclei, necrosis, anisonucleosis, irregular bordered fragments, absent cytoplasmic collar, and peripheral palisading. High nucleus-to-cytoplasm ratio, irregular nuclear borders, and homogeneous cytoplasm (combination sensitivity of 59% and specificity of 100%) were the best predictive features for LGUC. Minor predictive criteria were eccentric nuclei and nuclear molding. ThinPrep provides well preserved, cleaner specimens without significantly altering the morphology. The three key criteria applied in cytospin specimens to diagnose LGUC were reproducible in ThinPrep specimens. Diagn. Cytopathol. 2003;29:125,129. © 2003 Wiley-Liss, Inc. [source]

Gemcitabine induced digital ischaemia and necrosis

EUROPEAN JOURNAL OF CANCER CARE, Issue 3 2010
A. HOLSTEIN md
HOLSTEIN A., BÄTGE R. & EGBERTS E.-H. (2010) European Journal of Cancer Care19, 408,409 Gemcitabine induced digital ischaemia and necrosis A 70-year-old woman presented with a 7-day history of severe pain, paresthesia, oedema, acrocyanosis and punctate haemorrhagic lesions on her fingertips. The complaints began 2 days after the second cycle of a first-line chemotherapy consisting of cisplatin or carboplatin, and gemcitabine due to advanced urothelial carcinoma. At the fingertips of both hands, haemorrhagic and partly ulcerative lesions were found; these were attributed to vascular toxicity of gemcitabine. Therapeutically sympathicolysis by bilateral blockade of the brachial plexus was performed, accompanied by intravenous administration of the prostacyclin analog iloprost, fractionated heparin subcutaneously and oral therapy with corticosteroids and aspirin. Digital amputation could be avoided. Acral ischemia is a rare but probably underreported adverse effect of gemcitabine therapy and a potential source of misdiagnosis. [source]

Papillary urothelial carcinoma in sigmoid neobladder suggesting ,intraluminal seeding' from ureter cancer

INTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2008
Naoki Kawamorita md
No abstract is available for this article. [source]

Micturitional disturbance due to labial adhesion as a cause of vaginal implantation of bladder urothelial carcinoma

INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2006
SATOSHI OGISO
Abstract, Vaginal implantation of urinary tract urothelial carcinoma is a rare finding, with few cases reported in the literature. This is the first reported case of vaginal implantation of bladder urothelial carcinoma thought to be due to micturitional disturbances secondary to labial adhesion. The authors propose that implantation via pooled urine in the vagina may have occurred, and suggest that labial adhesion be treated in patients with urinary tract urothelial carcinoma, even if asymptomatic. [source]

High incidence of and risk factors for metachronous bilateral upper tract urothelial carcinoma in Taiwan

Concurrent diagnosis of urothelial carcinoma and squamous cell carcinoma of the bladder in a patient with a vesicorectal fistula from invasive rectal cancer

INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2006
KOICHI KODAMA
Abstract, A 47-year-old man underwent a low anterior resection of the rectosigmoid colon with en bloc cystoprostatectomy for vesicorectal fistula due to a locally advanced rectal cancer. Histopathological examination of the bladder revealed two additional primary malignancies: urothelial carcinoma and squamous cell carcinoma. To our knowledge, this is the first reported case of two histologically distinct urothelial malignancies that were diagnosed during a work up of vesicorectal fistula due to adenocarcinoma of the rectum. [source]

FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer,

THE JOURNAL OF PATHOLOGY, Issue 1 2007
DC Tomlinson
Abstract FGFR3 is frequently activated by mutation in urothelial carcinoma (UC) and represents a potential target for therapy. In multiple myeloma, both over-expression and mutation of FGFR3 contribute to tumour development. To define the population of UC patients who may benefit from FGFR-targeted therapy, we assessed both mutation and receptor over-expression in primary UCs from a population of new patients. Manual or laser capture microdissection was used to isolate pure tumour cell populations. Where present, non-invasive and invasive components in the same section were microdissected. A screen of the region of the highest tumour stage in each sample yielded a mutation frequency of 42%. Mutations comprised 61 single and five double mutations, all in hotspot codons previously identified in UC. There was a significant association of mutation with low tumour grade and stage. Subsequently, non-invasive areas from the 43 tumours with both non-invasive and invasive components were analysed separately; 18 of these had mutation in at least one region, including nine with mutation in all regions examined, eight with mutation in only the non-invasive component and one with different mutations in different regions. Of the eight with mutation in only the non-invasive component, six were predicted to represent a single tumour and two showed morphological dissimilarity of fragments within the block, indicating the possible presence of distinct tumour clones. Immunohistochemistry showed over-expression of FGFR3 protein in many tumours compared to normal bladder and ureteric controls. Increased expression was associated with mutation (85% of mutant tumours showed high-level expression). Overall, 42% of tumours with no detectable mutation showed over-expression, including many muscle-invasive tumours. This may represent a non-mutant subset of tumours in which FGFR3 signalling contributes to the transformed phenotype and which may benefit from FGFR-targeted therapies. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Undifferentiated carcinoma of the renal pelvis with osteoclast-like giant cells: a report of two cases

APMIS, Issue 5 2010
SAMUEL I. MCCASH
McCash SI, Unger P, Dillon R, Xiao G-Q. Undifferentiated carcinoma of the renal pelvis with osteoclast-like giant cells: a report of two cases. APMIS 2010; 118: 407,12. Undifferentiated carcinoma with osteoclast-like giant cells arising in the urothelium of the bladder or upper urinary tract is an extremely rare entity. The majority of cases found in the renal pelvis and bladder are associated with either an in situ urothelial malignancy or a conventional high-grade urothelial carcinoma. These malignancies tend to behave poorly with a grim prognosis and course. We report two additional cases of undifferentiated carcinoma with osteoclast-like giant cells of the renal pelvis in two patients disease free 42 and 18 months after surgical treatment, respectively. [source]

Overexpression of cyclooxygenase-2 in urothelial carcinoma in conjunction with tumor-associated-macrophage infiltration, hypoxia-inducible factor-1, expression, and tumor angiogenesis

APMIS, Issue 3 2009
WAN-TZU CHEN
This study examines whether the expression of cyclooxgenase-2 (COX-2) in urothelial carcinoma (UC) is associated with macrophage infiltration, hypoxia-inducible factor-1, (HIF-1,) expression and angiogenesis. We investigated the expression of COX-2 associated with HIF-1, and performed double immunohistochemical analysis of 216 UCs for COX-2 expression and the correlation with tumor-associated-macrophage (TAM) density and microvessel density (MVD) in situ. A high expression of COX-2 was positively correlated with tumor invasiveness, histologic grade and HIF-1, expression in UC (p<0.0001, p=0.003, p<0.0001, respectively). Quantification of double staining of COX-2/CD34 and COX-2/CD68 showed that a higher MVD and TAM density was found in COX-2 high-expression than in COX-2 low-expression tumor fields (p<0.0001). Adjacent to the principal of COX-2 expression areas, MVD value and TAM density were significantly increased in HIF-1, high-expression specimens compared with HIF-1, low-expression ones (p<0.0001). Interestingly, our data revealed that high COX-2 expression (p=0.002), high HIF-1, expression (p<0.0001) and TAM density (p<0.0001) were all associated with high MVD value. Our results suggest that COX-2 may produce a cooperative effect in promoting tumor progression and may be involved in the process of angiogenesis through increasing TAM infiltration or HIF-1, regulation by hypoxia. [source]

Molecular characterization of upper urinary tract tumours

BJU INTERNATIONAL, Issue 6 2010
Laura Izquierdo
OBJECTIVES To assess gene-expression patterns of BIRC5, FGFR3, IGF2, KRT20, UPK2, EBF1, CDH1, FXYD3, HTERT, TP53, AGR2, HER2 and VEGF, widely known markers of bladder urothelial carcinoma (UC) in upper tract UC, and to determine their value as prognostic factors of tumour progression and cancer-specific survival. PATIENTS AND METHODS The study included 83 formalin-fixed paraffin-embedded tissue specimens (68 and 15 from patients with UTUC and controls, respectively) collected between 1990 and 2004. Thirteen bladder cancer-related genes were selected from previous reports and analysed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) in all samples. RESULTS Six genes were over-expressed (BIRC5, FGFR3, KRT20, UPK2, FXYD3 and hTERT) and three under-expressed (AGR2, TP53 and VEGF) in the tumour group (P < 0.05). For four genes (IGF2, EBF1, CDH1 and HER2) there was no statistically significant difference between the tumour and control groups. Overall, 21 patients developed tumour progression and 13 died from UTUC after a mean follow-up of 35.24 months. The 5-year disease-free progression and cancer-specific survival rates were 65.8% and 72.9%, respectively. In a multivariate regression analysis, the independent predictive variable for tumour progression and cancer-specific survival was pathological stage (hazard ratio 3.60, P < 0.001; and 3.73, P < 0.005, respectively), but none of the studied genes were identified as prognostic factors of tumour progression or cancer-specific survival. CONCLUSIONS Our data suggest that bladder cancer and UTUC share some characteristics, but have differences in gene expression. None of BIRC5, FGFR3, IGF2, KRT20, UPK2, EBF1, CDH1, FXYD3, HTERT, TP53, AGR2, HER2 and VEGF were correlated either tumour progression or survival. [source]

Glucose-regulated protein 78 expression in urothelial carcinoma of the upper urinary tract

BJU INTERNATIONAL, Issue 6 2010
Kenji Uematsu
OBJECTIVE To examine glucose-regulated protein 78 (GRP78; a major molecular chaperone at the endoplasmic reticulum, strongly expressed in several tumours) expression in urothelial carcinoma (UC) of the upper urinary tract (UUT) and to evaluate the diagnostic and progressive importance of GRP78 expression in UC-UUT. PATIENTS AND METHODS We investigated GRP78 expression (using immunohistochemistry) in 126 UC-UUTs to assess its relevance to progression. GRP78 overexpression was recognised in 23 (18.3%) of tumour samples. RESULTS There was no association between GRP78 overexpression and clinicopathological findings, except for an association with low grade in invasive tumours. GRP78 overexpression significantly improved the disease-free survival rate in all patients (according to univariate and multivariate analyses), but did not alter the overall survival rate. CONCLUSION The detection of GRP78 overexpression would appear to provide valuable information for the prognosis of UC-UUT. [source]

A delay in radical nephroureterectomy can lead to upstaging

BJU INTERNATIONAL, Issue 6 2010
Matthias Waldert
Study Type , Prognosis (case series) Level of Evidence 4 OBJECTIVE To examine the association between the delay from diagnosis of upper-tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU), and the pathological features and outcomes, as the decision to proceed to RNU for an individual patient is complex. PATIENTS AND METHODS The records of 187 patients who had RNU were reviewed; the interval from diagnosis to RNU was analysed as both a continuous (months) and categorical variable (<3 vs ,3 months). Logistic regression and survival analyses were used to evaluate the association between time from diagnosis to RNU with pathological characteristics and clinical outcomes. RESULTS The median time from diagnosis to RNU was 45 days (interquartile range 68). A delay from diagnosis to RNU analysed as a continuous variable was associated with advanced stage, higher grade, previous endoscopic procedure, tumour necrosis, infiltrative tumour architecture, and lymphovascular invasion (P = 0.034), but not disease recurrence or cancer-specific mortality. In the subgroup of patients (90, 48.1%) who had muscle-invasive disease (,pT2) a longer delay from diagnosis to RNU as a continuous variable was associated with advanced stage (P = 0.030), higher grade (P = 0.014), infiltrative tumour architecture (P = 0.044), lymphovascular invasion (P = 0.034), disease recurrence (P = 0.02), and cancer-specific mortality (P = 0.03). CONCLUSIONS Our data suggest that a delay in the interval from diagnosis to RNU is associated with more advanced disease stage. These findings might have important implications for trial design in the ongoing evaluation of neoadjuvant regimens. Timely consideration of definitive treatment for patients with high-risk UTUC is of high importance. Further studies are necessary to validate these hypothesis-generating findings. [source]

The presence of lymphovascular invasion in radical cystectomy specimens from patients with urothelial carcinoma portends a poor clinical prognosis

BJU INTERNATIONAL, Issue 8 2008
Daniel Canter
OBJECTIVES To assess the prognostic significance of lymphovascular invasion (LVI) on clinical outcomes in patients with transitional cell carcinoma of the bladder treated with radical cystectomy (RC). PATIENTS AND METHODS We retrospectively evaluated a prospectively maintained and authorised cystectomy database; the presence or absence of LVI was determined by pathological examination of the RC specimen. Cox regression analysis and Kaplan-Meier tables were developed to evaluate the contribution of LVI to clinical outcomes. RESULTS In all, we analysed 356 patients treated with RC and urinary diversion between 1988 and 2006, with a mean follow-up of 45.6 months. Of these patients, 242 (68%) had no evidence of LVI in the RC specimen, whereas 114 (32%) had LVI. Patients with LVI tended to present with higher pathological stage; 84 (74%) had pT3 or pT4 disease. On univariable analysis the presence of LVI conferred a significant risk for decreased overall, cancer-specific and recurrence-free survival (P < 0.001); the mean values for LVI-negative patients were 96.8, 157.4, and 135.0 months, respectively, vs LVI-positive patients, whose survival times were 52.3, 82.7 and 75.2 months, respectively. The multivariable analysis showed significant independent risk for cancer-specific and overall survival for patients who were LVI-positive and had no lymph-node metastases. The hazard ratios (95% confidence interval) were 1.63 (1.06,2.51, P < 0.026) and 1.81 (1.06,3.08, P < 0.03) for overall and disease-specific survival, respectively. CONCLUSIONS The presence of LVI in the pathological RC specimen confers significant independent risk for reduced bladder cancer-specific and overall survival. This variable could be used to prospectively stratify patients who would benefit from adjuvant chemotherapy. [source]

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma

BJU INTERNATIONAL, Issue 4 2005
Elli Ioachim
OBJECTIVE To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. MATERIALS AND METHODS Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27,89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTS Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. CONCLUSION Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression. [source]

Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence

BJU INTERNATIONAL, Issue 4 2003
M.G. Friedrich
OBJECTIVE To investigate the effect of cyclooxygenase-2 (COX-2) on microvessel density (MVD) and on the clinical prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder, as COX-2 expression is significantly greater in epithelial tumours and there is increasing evidence that COX-2 might contribute to tumour neovascularization. PATIENTS AND METHODS We assessed tumour samples from 110 patients undergoing transurethral resection for primary pTa/pT1 bladder carcinoma (pTa, 84; pT1, 26; grade 1, 22; grade 2, 81; grade 3, seven). Paraffin sections were assessed immunohistochemically using antibodies against COX-2, CD34 (endothelial cells) and CD105 (proliferating vessels). COX-2 expression was quantified by the number of stained cells (negative, +, ++) and the MVD calculated as vessels per field. RESULTS Of the 110 tumours, 45 (41%) had no immunostaining for COX-2, 40 had faint staining with at least isolated positive cells (+) and 25 stained ++. COX-2 positive tumours had significantly greater vascularization for proliferating vessels. In COX-2 negative tumours the MVD was 22.1, identified by CD34 immunostaining, and 3.4 for proliferating vessels (CD105), whereas COX-2 positive tumours had a MVD of 18.3 (CD34), and of 5.8, respectively (CD105). Complete follow-up data were available in 91 patients; after a mean follow-up of 25 months, 18 (20%) had tumour recurrences. There was no significant difference in the recurrence rates or disease-free survival between COX-2-positive (19%, 25.6 months) or -negative patients (21%, 25.2 months). CONCLUSION These results confirm the involvement of COX-2 in angiogenesis in bladder cancer, as COX-2 promoted blood vessel proliferation in the tumour zone, and indicate the usefulness of COX-2-inhibiting drugs in preventing and treating superficial bladder cancer. [source]

Telomerase activity as a potential marker in preneoplastic bladder lesions

BJU INTERNATIONAL, Issue 4 2000
F. Lancelin
Objective To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. Patients and methods Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. Results Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable ,telomerase inhibitor'. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive. Conclusion These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression. [source]

Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium,

CANCER, Issue 8 2004
A trial of the Eastern Cooperative Oncology Group
Abstract BACKGROUND The regimens of carboplatin plus paclitaxel (CP) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) were compared in patients with advanced urothelial carcinoma. METHODS Patients with metastatic urothelial carcinoma were randomized to receive either CP (paclitaxel at a dose of 225 mg/m2 and carboplatin [targeted area under the concentration-time curve (AUC) of 6] given every 21 days) or the standard M-VAC dosage. RESULTS Eighty-five patients were randomized to the respective treatment regimens (41 to CP and 44 to M-VAC). Response rates and overall survival were similar for both treatment arms. Patients treated with CP had an overall response rate of 28.2% (95% binomial confidence interval, 15.0,44.9%) compared with an overall response rate of 35.9% for the M-VAC arm (95% binomial confidence interval, 21.2,52.8%) (P = 0.63, Fisher exact test). The median progression-free survival among patients who were treated with M-VAC was 8.7 months and was 5.2 months for patients receiving CP (P = 0.24, log-rank test). At a median follow-up of 32.5 months, the median survival for patients treated with M-VAC was 15.4 months versus 13.8 months for patients treated with CP (P = 0.65, log-rank test). Patients treated with M-VAC were found to have more severe worst-degree toxicities compared with patients treated with CP (P = 0.0001). There were no significant differences with regard to quality of life as assessed by the Functional Assessment of Cancer Therapy,Bladder (FACT-BL) instrument (P = 0.33). CONCLUSIONS Interpretation of the results of this study must be made with caution because the study failed to reach its accrual goal. Patients treated with CP had a median survival of 13.8 months compared with 15.4 months for patients treated with M-VAC. Patients treated with CP appeared in general to better tolerate their treatment; however, there were no significant differences noted with regard to measured quality of life parameters. Cancer 2004. © 2004 American Cancer Society. [source]

A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinoma

CANCER, Issue 9 2003
Barbara J. Gitlitz M.D.
Abstract BACKGROUND The objectives of the current study were to evaluate the safety and efficacy of gemcitabine plus docetaxel in patients with unresectable (Stage T4 or , N1) metastatic or locally advanced transitional cell carcinoma (TCC) of the urothelial tract. METHODS A total of 27 patients were enrolled in the current multisite study, which was performed within the University of California-Los Angeles Community Oncology Research Network. The first 10 patients in the study received 800 mg/m2 of gemcitabine intravenously on Days 1, 8, and 15 of a 28-day treatment cycle. In addition, on Day 1, the first 10 patients received 80 mg/m2 of docetaxel intravenously after completion of the gemcitabine infusion. Because of dose-limiting toxicity (neutropenia), the initial dose of docetaxel was reduced to 60 mg/m2 for the remaining patients who entered the study (n = 17 patients). RESULTS Neutropenia was the most common adverse event that occurred in patients at the Grade 3 level (in 10 of 27 patients; 37.0%) and the Grade 4 level (in 6 of 27 patients; 22.2%). There were no other adverse events at the Grade 4 toxicity level. Twenty-five of 27 patients (92.6%) completed more than 1 cycle of combination therapy and were evaluated for antitumor responses. The frequency of objective clinical responses was 33.3% (9 of 27 patients). Complete responses to therapy were observed in 2 of 27 patients (7.4%), and partial responses were observed in 7 of 27 patients (25.9%). The median duration of response was 20 weeks (range, 12+ weeks to 152 weeks). The median survival duration was 52 weeks (range, 12 weeks to 160+ weeks). Four of 27 patients (14.8%) remained alive at the time of the current data analysis. CONCLUSIONS The results of the current study suggested that combination therapy with gemcitabine and docetaxel was an effective treatment for patients with unresectable (Stage T4 or , N1) metastatic or locally advanced TCC of the urothelial tract. Gemcitabine plus docetaxel appeared to be tolerated well, and treatment-related toxicities were limited to hematologic toxicities. Because cisplatin-containing regimens are contraindicated for patients with impaired renal function, the gemcitabine plus docetaxel combination may prove to be an effective and well tolerated treatment option for these patients. Cancer 2003. © 2003 American Cancer Society. [source]

Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum-based regimens

CANCER, Issue 7 2002
Sergio Ricci M.D.
Abstract BACKGROUND The objective of this study was to evaluate the efficacy and toxicity of gemcitabine plus epirubicin in previously untreated patients with advanced urothelial carcinoma who were not eligible for cisplatin-based regimens. METHODS Patients with advanced urothelial carcinoma and at least one of the following characteristics were eligible: impaired renal function (creatinine clearance < 60 mL per minute), an Eastern Cooperative Oncology Group performance status (PS) , 2, and age , 75 years. The treatment included epirubicin 70 mg/m2 as an intravenous bolus on Day 1 and gemcitabine 1000 mg/m2 over 30 minutes on Days 1 and 8 of a 21-day cycle. RESULTS Thirty-eight patients entered the study, and a total of 152 cycles were administered, with a median of 4 cycles per patient (range, 1,6 cycles per patient). The following Grade 3,4 hematologic toxicities were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed. Dose intensities of epirubicin and gemcitabine were 19.6 mg/m2 per week (84%) and 532.2 mg/m2 per week (80%), respectively. There were 2 complete responses (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%), and 12 patients with progressive disease (31.6%), for an overall response rate of 39.5% (95% confidence interval, 25.1,55.1). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months, respectively. The 1-year survival rate was 38%, and the median PFS and OS were 6.4 months and 16.4 months, respectively, in patients with PS 0,1. Thirty patients were symptomatic: Seventeen patients (56.7%) achieved a complete response, and 5 patients (16.7%) achieved a partial symptomatic response. CONCLUSIONS At the doses given in this study, gemcitabine and epirubicin had a good tolerability profile with interesting activity in patients with advanced urothelial carcinoma who were not fit for cisplatin-based regimens. Cancer 2002;95:1444,50. © 2002 American Cancer Society. DOI 10.1002/cncr.10860 [source]

Precise microdissection of human bladder carcinomas reveals divergent tumor subclones in the same tumor

CANCER, Issue 1 2002
Liang Cheng M.D.
Abstract BACKGROUND Human bladder carcinoma is thought to arise from a field change that affects the entire urothelium. Whether independently transformed urothelial cell populations exist in the same patient is uncertain. METHODS We studied the clonality of urinary bladder carcinoma in 18 female patients who underwent cystectomy for urothelial carcinoma. None had multiple tumors. Tumor samples were obtained from different areas of the same tumor. Sixty-seven tumor samples were analyzed. Tumor genomic DNA was microdissected and extracted from formalin-fixed, paraffin-embedded slides. The clonality of urothelial tumors was evaluated on the basis of a polymorphism of the X chromosome-linked human androgen receptor gene (HUMARA) locus. The technique is dependent on digestion of DNA with the methylation-sensitive restriction enzyme HhaI, polymerase chain reaction (PCR) amplification of HUMARA locus, and detection of methylation of this locus. With this method, only the methylated HUMARA allele is selectively amplified by PCR. RESULTS Eleven of 18 patients were informative. Nonrandom inactivation of the X chromosome was found in 9 of the 11 informative patients (82%). Seven patients showed different patterns of nonrandom X chromosome inactivation for tumor samples obtained from different regions of the same tumor. Two patients showed the same pattern of nonrandom X chromosome inactivation in all samples. CONCLUSIONS Some muscle-invasive urothelial carcinomas may arise from independently transformed progenitor urothelial cells, supporting the "field effect" theory for bladder carcinogenesis. Cancer 2002;94:104,10. © 2002 American Cancer Society. [source]

Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevance

HISTOPATHOLOGY, Issue 5 2007
S Langbein
Aims:, Lectins, and especially galectins, appear to be important in malignancy-associated processes. The aim was to analyse comprehensively the presence of galectins in urothelial tumours. Methods and results:, Non-cross-reactive antibodies against seven family members from the three subgroups (prototype: galectin-1, -2 and -7; chimera type: galectin-3; tandem-repeat type: galectin-4, -8 and -9) were used. Gene expression was monitored in specimens of normal urothelium, fresh tumour tissue and cell lines by real-time polymerase chain reaction (PCR). The presence and evidence of tumour-associated up-regulation were shown for galectin-1 and -3. This was less clear-cut for galectin-4 and -8. Galectin-7 was expressed in all cell lines; galectin-2 and -9 were detected at comparatively low levels. Galectin-2, -3 and -8 up-regulation was observed in superficial tumours, but not in muscle-invasive tumours (P < 0.05). Immunoreactivity correlated with tumour grading for galectin-1, -2 and -8, and disease-dependent mortality correlated with galectin-2 and -8 expression. Binding sites were visualized using labelled galectins. Conclusions:, The results demonstrate a complex expression pattern of the galectin network in urothelial carcinomas. Galectin-1, -2, -3 and -8 are both potential disease markers and also possible targets for bladder cancer therapy. [source]

Somatic mutations of adenomatous polyposis coli gene and nuclear b-catenin accumulation have prognostic significance in invasive urothelial carcinomas: Evidence for Wnt pathway implication

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2009
Efstathios Kastritis
Abstract Wnt pathway signaling is crucial in many cancers and data indicate crosstalk with other key cancer pathways, however in urothelial carcinogenesis it has not been extensively studied. We searched for mutations in adenomatous polyposis coli (APC), a key regulator of the pathway, and studied b-catenin expression and interactions with the expression of other markers of apoptosis, angiogenesis, and proliferation in patients with invasive urothelial cancer. The mutation cluster region of APC was directly sequenced in 70 patients with muscle invasive disease who were treated with surgery and adjuvant chemotherapy. COX-2, p53, Ki67, and b-catenin were studied immunohistochemically and micro vessel density was quantified by CD105 expression. Single somatic amino-acid substitutions (missense) were found in 9 (13%) and frameshift deletions in 2 (3%) tumors, all located in regions adjacent to b-catenin binding sites. Patients having either APC missense mutations or b-catenin nuclear accumulation had less frequent COX-2 overexpression (24% vs. 76%, p = 0.043) and more frequent lymph node involvement (75% vs. 38%, p = 0.023). Patients with either APC mutations or b-catenin accumulation had shorter disease-free interval (13.4 vs. 28 months, p = 0.07), whereas in multivariate analysis they had shorter disease-specific survival (60.5 vs. 20.6 months, p = 0.048). Somatic APC missense mutations are not rare in advanced urothelial neoplasms. Either APC mutations and/or aberrant expression of b-catenin are associated with worse outcome. Further study of the role of the Wnt pathway, potential crosstalk with other pathways and potential candidate therapeutic targets in urothelial cancer is needed. © 2008 Wiley-Liss, Inc. [source]

Microscopic hematuria as a screening marker for urinary tract malignancies

INTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2001
Kazunobu Sugimura
Abstract Background: Although a mass screening urinalysis is a widely accepted procedure, it has not yet been shown if microhematuria is an appropriate and useful screening marker for urologic malignancies. Methods: (1) The incidence of hematuria was studied in 113 patients with renal cell carcinoma (RCC), 185 with bladder carcinoma and 51 with renal pelvic or ureteral carcinoma. The association of the T stage with the intensity of hematuria in each malignancy was also examined. (2) In 823 asymptomatic adults with microhematuria, the prevalence of these malignancies was studied retrospectively to find the positive predictive value (PPV). Results: (1) The incidence of hematuria was 35% for RCC, including gross and microhematuria. Advanced RCC (T3 and T4) were diagnosed more frequently in the gross hematuria group than in the microhematuria and no hematuria groups. In contrast, the incidence of hematuria was 94% for urothelial carcinomas either in the upper urinary tract or in the bladder. There was no significant difference in the T stage nor grade between the gross hematuria group and the microhematuria group. (2) Regarding asymptomatic microhematuria, the PPV was 1.7% (14 cases) for bladder carcinoma, 0.4% (3 cases) for ureteral/renal pelvic carcinoma and 0.2% (2 cases) for RCC. In men aged 50 years or older, PPV was 6.2% for urothelial carcinomas. In 14 cases of bladder carcinoma, 3 cases showed muscle invasion. Conclusions: Microhematuria is an appropriate screening marker for urothelial carcinomas, particularly in elderly men, but not for RCC. However, it is unlikely that a mass screening urinalysis using a single voided urine sample would contribute to earlier detection of bladder carcinoma. [source]

hTERT expression in sporadic renal cell carcinomas

THE JOURNAL OF PATHOLOGY, Issue 2 2001
Valérie Paradis
Abstract Human telomerase is a specialized reverse transcriptase that catalyses telomeric repeat addition at the ends of chromosomes. Activation of this enzyme is one of the key steps in cell immortalization and carcinogenesis, and one of its components, hTERT, is considered as the rate-limiting factor. While telomerase activity was found to be prognostically relevant in various cancers, results obtained from renal cell carcinomas (RCC) failed to show any correlation with the usual prognostic factors. The aim of the study was to reassess the role of telomerase and its hTERT component in the biological behaviour of RCC using new quantitative techniques, such as the quantitative evaluation of hTERT mRNA level by a real-time RT-PCR procedure and the mesuring of telomerase activity by an ELISA TRAP assay. Since experimental evidence supports a relationship between cell proliferation or c-myc expression and telomerase, the proliferation index and c-myc mRNA levels were also studied. Forty-one RCC (29 conventional renal cell carcinomas (CRCC), 10 papillary RCC and two urothelial carcinomas) were studied. In 73% of cases, normalized hTERT mRNA expression was significantly higher in the tumour sample than in the normal tissue. Telomerase activity was detected in 63% of RCC, while corresponding normal tissue was always negative. Analysis of correlations showed firstly that both telomerase activity and hTERT mRNA level were lower in the group of CRCC versus non-CRCC (TRAP: 0.3±0.1 versus 0.6±0.2, p<0.05; hTERT/PO mRNA: 5±3 versus 37±8, p<0.001, respectively); secondly, that in the group of CRCC, hTERT mRNA expression level was correlated with the stage of the tumour (p=0.01); and thirdly, that no correlation was observed between c-myc mRNA level and hTERT mRNA level. In conclusion, these results support the involvement of telomerase in RCC and the potential interest of hTERT mRNA quantification. Copyright © 2001 John Wiley & Sons, Ltd. [source]