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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Bladder Cancer - July 2002
National Cancer Institute®
Last Modified: July 1, 2002
- Superficial bladder tumors in patients under 40 years of age: clinical, prognostic and cytogenetic aspects.
- Genetic aberrations of NAT2 and chromosome 8: their association with progression in transitional cell carcinoma of the urinary bladder.
- Coding criteria of bladder cancer: effects on estimating survival.
- [Loss of heterozygosity fine mapping of chromosome 17p13 in transitional cell carcinoma of human urinary bladder]
- Reliability of MR imaging-based virtual cystoscopy in the diagnosis of cancer of the urinary bladder.
- Are dedicated bladder films necessary as part of intravenous urography for haematuria?
- Gender- and smoking-related bladder cancer risk.
- Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder cancer.
- Transitional cell carcinoma of the bladder in young adults: presentation, natural history and outcome.
- Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with
- Tobacco use and occupational exposure to carcinogens, but not N-acetyltransferase 2 genotypes are major risk factors for bladder
- Expression of pS2 protein and its relation with the Ki-67 proliferative indices and tumor recurrence in superficial bladder carcinomas.
- Amsacrine and cisplatin in poor prognosis patients with metastatic transitional cell carcinoma of the urothelium: a phase-II study.
- Foods and risk of bladder cancer: a case-control study in Uruguay.
- Splice variants but not mutations of DNA polymerase beta are common in bladder cancer.
- Locally advanced and metastatic bladder cancer.
- The genetic alterations in the oncogenic pathway of transitional cell carcinoma of the bladder and its prognostic value.
- P53 codon 72 polymorphism in bladder cancer--no evidence of association with increased risk or invasiveness.
- Lack of evidence for the association of tumor necrosis factor-alpha gene promoter polymorphism with calcium oxalate stone and bladder cancer
- Nonbilharzial bladder carcinoma complicating pregnancy: review of the literature.
- Bladder adenocarcinoma: 31 reported cases.
- Deficiency of a novel mismatch repair activity in a bladder tumor cell line.
- Bladder cancer incidence in the world.
- HRAS1 variable number of tandem repeats polymorphism and risk of bladder cancer.
- Protamine-fragment peptides fused to an SV40 nuclear localization signal deliver oligonucleotides that produce antisense effects in prostate and
- Prognostic significance of atypical papillary urothelial hyperplasia.
- Kinetic profiles by topographic compartments in muscle-invasive transitional cell carcinomas of the bladder: role of TP53 and NF1 genes.
- [ALA fluorescent diagnosis of bladder cancer]
- Pooled analysis and meta-analysis of glutathione S-transferase M1 and bladder cancer: a HuGE review.
- Stage specific follow-up strategy after cystectomy for carcinoma of the bladder.
- The effects of the current World Health Organization/International Society of Urologic Pathologists bladder neoplasm classification system
- Bladder tumor markers for monitoring recurrence and screening comparison of hyaluronic acid-hyaluronidase and BTA-Stat tests.
- [Clinico-pathologic differences between bladder neoplasm with low malignant potential and low-grade carcinoma]
- Motility is rate-limiting for invasion of bladder carcinoma cell lines.
- [Fluorescent endoscopy superior to white light endoscopy. Detecting cancers of the urinary bladder earlier]
- [Clinical course and mid- and long-term prognosis of superficial bladder tumors]
- [Survival in patients treated with radical cystectomy for bladder carcinoma]
- Distressful symptoms after radical radiotherapy for urinary bladder cancer.
- Microsatellite instability at tetranucleotide repeats in skin and bladder cancer.
Table of Contents
1
UI - 11598450
AU - Iori F; De Dominicis C; Liberti M; Frioni D; Vahedi M; Leonardo C; De
TI -
Nunzio C; Laurenti C
Superficial bladder tumors in patients under 40 years of age: clinical,
prognostic and cytogenetic aspects.
SO - Urol Int 2001;67(3):224-7
AD - Department of Urology U. Bracci (IIIrd Division, Dir. Prof. C.
Laurenti), University of Rome La Sapienza, Viale Regina Elena, I-00161
Rome, Italy.
Bladder carcinoma with transitional cells is the most frequent neoplasia
in the urinary system, but it is quite rare in patients under 40 years
of age (0.4-2%). An analysis of 21 patients under 40 and a review of
other reports show that tumors in patients under 20 years old have
little tendency to recur and to progress, while tumors in patients aged
between 21 and 40 have a behavior pattern similar to older age groups
regarding recurrence and disease progression. Preliminary results of a
study using fluorescent in situ hybridization with probes for the
centromere of chromosomes 7 and 17 showed a high incidence of aneusomy
with regard to these chromosomes and a genetic difference between
superficial tumors in the young and in adults. Using probes from
chromosomes already described in bladder carcinogenesis, we obtained
higher sensitivity and specificity in detecting aneuploid events.
Copyright 2001 S. Karger AG, Basel
2
UI - 11598453
AU - Watters AD; Stacey MW; Going JJ; Grigor KM; Cooke TG; Sim E; Bartlett JM
TI -
Genetic aberrations of NAT2 and chromosome 8: their association with
progression in transitional cell carcinoma of the urinary bladder.
SO - Urol Int 2001;67(3):235-9
AD - Department of Surgery, Glasgow Royal Infirmary, University of Glasgow,
Glasgow G31 2ER, UK. adw10q@clinmed.gla.ac.uk
INTRODUCTION/OBJECTIVE: N-acetyltransferase 2 (NAT2), mapped to 8p22, is
a polymorphic enzyme which metabolizes aromatic amines. Loss of
heterozygosity of 8p22 is associated with an increased risk of bladder
cancer. This study evaluated NAT2 and chromosome 8 in sequential tumours
from bladder cancer patients to determine if NAT2 alterations increase
the risk of progression. MATERIALS AND METHODS: Thirty-seven sequential
carcinomas from 19 patients were assessed using fluorescence in situ
hybridization. RESULTS: Five carcinomas showed loss of NAT2; 4 of these
were from pTa/pT1 tumours. Polysomy 8 was observed in 4 of 14 (29%)
primary carcinomas (pTa/pT1), in 4 of 12 (33%) pTa/pT1 recurrences, and
in 90% (9/10) of the detrusor muscle invasive tumours (pT2+). 6 of 8
(75%) locally invasive tumours with polysomy 8 were from patients who
subsequently developed disease progression (pT2+). In total, 13.5%
(5/37) of the carcinomas were abnormal for NAT2, and 46% (17/37) were
abnormal for chromosome 8 copy number. Polysomy 8 was associated with
high grade (p = 0.01) and stage (p = 0.03) and disease progression (p =
0.03). CONCLUSION: Whilst there does not appear to be an association
between loss of NAT2 and risk of progression in transitional cell
carcinoma, the high rate of polysomy of chromosome 8 implies that other
genes on this chromosome significantly influence disease progression.
Copyright 2001 S. Karger AG, Basel
3
UI - 11695203
AU - Patriarca S; Gafa L; Ferretti S; Vitarelli S; Cesaraccio R; Crocetti E;
TI -
Ferrante MC; Rollo P; Tagliabue G
Coding criteria of bladder cancer: effects on estimating survival.
SO - Epidemiol Prev 2001;25(3 Suppl):42-7
AD - Registro Tumori Piemonte, Centro per l'epidemiologia e la prevenzione
oncologica, CPO Piemonte, Dipartimento di oncologia, Ospedale San
Giovanni antica sede, Torino. silvia.patriarca@asl1.to.it
The aim of this study is to evaluate the consistency between routine
methods for coding urinary bladder tumours in eight Italian cancer
registries and the European Network of cancer registries (ENCR)
criteria. Furthermore, it aims to evaluating the impact of the
discordance on survival data. Eight cancer registries took part in the
study: Ferrara, Florence, Macerata, Ragusa, Romagna, Sassari, Turin and
Varese. The first 100 cases of neoplasm of the urinary bladder incident
in the years 1993-1994 were identified from the files of each registry.
The original pathology reports were made available. A working group
considered eligible to the study 699 cases of microscopically confirmed
transitional carcinoma (ICD-O morphology code 812-813). Using the ENCR
criteria, each of these was classified according to morphology code
(8120 vs. 8130) and behaviour (1/ uncertain, /2 non-invasive, 3/
invasive). Information of tumour behaviour was classified as follows:
(i) present, when expressly stated in the original report, (ii)
deducible, when not expressly stated but suggested by the pathologist's
description, and (iii) absent, when impossible to determine on the basis
of the original pathology report. The working group classification of
tumour behaviour and the classification of the registry of origin were
compared. There was a full concordance in the case of complete agreement
on the morphology code, and partial concordance when only the invasive
or non-invasive behaviour code was agreed upon. As much as 92.5% cases
were microscopically confirmed. Tumour behaviour was expressly stated in
the original report of 69.2% cases, not stated but suggested by the
pathologist's description in 21.2% cases, and impossible to determine in
9.6%. Agreement between the panel and the registry of origin was
complete in 71.2% cases and partial in 12.3% while there was a complete
discordance in 16.5% cases. The panel interpreted as non-invasive 111
cases coded as invasive by the registry of origin. Conversely, it was
estimated that 24% cases included in incidence data were non-invasive.
This article discusses the impact of misclassification on survival data.
4
UI - 11953150
AU - Zheng S; Zhang J; Di X; Xiao Z; Wang D; Li C; He Z; Han N; Guo S; Cheng
TI -
S; Gao Y
[Loss of heterozygosity fine mapping of chromosome 17p13 in transitional
cell carcinoma of human urinary bladder]
SO - Zhonghua Yi Xue Za Zhi 2002 Feb 10;82(3):161-3
AD - Department of Etiology and Carcinogenesis, Cancer Institute (Hospital),
Peking Union Medical College and Chinese Academy of Medical Sciences,
Beijing 100021, China.
OBJECTIVE: To determine the frequency and common deletion region of
allelic losses on chromosome 17p13 in transitional cell carcinoma (TCC)
of human urinary bladder so as to provide clues for isolation of
candidate tumor suppressor genes associated with TCC of urinary bladder.
METHODS: Loss of heterozygosity (LOH) analysis was made on 44 samples of
surgically resected primary TCC by using 13 microsatellite markers to
map the regions frequently deleted on chromosome 17p13. The relationship
between the LOH in each locus and pathological grade and stage was
analyzed. RESULTS: Out of the 44 samples, 35 (79.5%) showed allelic loss
in at least one of the 17p13 loci. The highest frequency of LOH (41.4%,
12/29) was at D17S513 in 17p13.2, the second highest frequency of LOH
(40.5%, 17/42) was at D17S1308 in 17p13.3, and the lowest (14.3%, 4/28)
was at D17S261 in 17p13.1. The most frequent LOH loci were mainly
located in three regions: D17S695-D17S1308 in 17p13.3, D17S1533-D17S831
in 17p13.2, and TP53 in 17p13.1. Among them only the LOH frequency of
TP53 locus was positively correlated to the grade (chi(2) = 5.104, P <
0.05) and stage (chi(2) = 5.382, P < 0.05) of TCC of unrinary bladder.
CONCLUSION: In 17p13 region, except for TP53 gene, still exist two
candidate tumor suppressor genes located in D17S695-D17S1308 and
D17S1533-D17S831 involved in the carcinogenesis of TCC of urinary
bladder. LOH of TP53 locus may be one of the later events in TCC, and
LOH in 17p13.3 and 17p13.2 may be the early events of TCC of uninary
bladder.
5
UI - 12034625
AU - Lammle M; Beer A; Settles M; Hannig C; Schwaibold H; Drews C
TI -
Reliability of MR imaging-based virtual cystoscopy in the diagnosis of
cancer of the urinary bladder.
SO - AJR Am J Roentgenol 2002 Jun;178(6):1483-8
AD - Department of Radiology, Klinikum rechts der Isar der Technischen
Universitat Munchen, Ismaninger Str. 22, D-81675 Munich, Germany.
OBJECTIVE: Our purpose was to evaluate MR imaging-based virtual
endoscopy in patients with urinary bladder cancer compared with
conventional cystoscopy as the gold standard. SUBJECTS AND METHODS:
Twenty-five patients with urinary bladder cancer diagnosed on
conventional cystoscopy underwent MR imaging of the pelvis. Patients
were examined without external bladder filling or administration of IV
contrast medium. No medications were administered. The data obtained by
MR imaging were reconstructed for virtual endoscopy on a workstation.
The locations and sizes of tumors were individually determined and
compared with results of conventional cystoscopy. RESULTS: Twenty-four
patients were evaluated; one patient's examination was excluded from
analysis because of metallic artifacts. Seventeen patients were
diagnosed with a single bladder tumor. Five patients had two tumors
each, and two patients had three tumors. Tumor diameter ranged from 0.4
to 6.4 cm. Thirty (90.9%) of 33 tumors detected on cystoscopy were
visualized with virtual endoscopy. The detection rate for 23 tumors of 1
cm or greater was 100%. Difficult conditions for conventional
cystoscopy, including hematuria, anterior wall involvement, and urethral
strictures, had no deleterious impact on virtual cystoscopy.
Difficulties in detection on virtual endoscopy were associated with flat
bladder tumors with minimal surface elevation. CONCLUSION: The results
of this study suggest a high reliability in the diagnosis of urinary
bladder cancer by MR imaging-based virtual cystoscopy-a noninvasive
method, independent of medication or contrast enhancement, that may be
of value for screening, primary diagnosis, and surveillance. Virtual MR
cystoscopy may be indicated when conventional cystoscopy cannot be
performed or is ineffective.
6
UI - 10792157
AU - Corrigan NT; Crooks J; Shand J
TI -
Are dedicated bladder films necessary as part of intravenous urography
for haematuria?
SO - BJU Int 2000 May;85(7):806-10
AD - Departments of Radiology and Urology, Stobhill General Hospital,
Glasgow, UK.
OBJECTIVE: To determine the use and assess the value of full-bladder
films during intravenous urography (IVU) which, despite the widespread
availability of flexible cystoscopy, remain part of IVU in many
radiology departments. Materials and methods A telephone survey of all
Scottish radiology departments where IVU is regularly used showed that
half routinely included a full-bladder film in the series. The reports
of all IVU over 2 years in the authors' department were analysed
retrospectively. The index urogram of all patients with bladder tumours
confirmed during this period was reviewed independently by three
observers, and together with the initial radiological reports was
correlated with the cystoscopic and histological findings. RESULTS: From
2625 patients, 139 (5.2%) IVU reports commented on the bladder; 1423
patients presented with no haematuria. None of the patients without
haematuria, where a comment was made about the bladder, had pathological
evidence of a tumour. Overall 121 of 464 (26%) new bladder tumours were
diagnosed on IVU before cystoscopy. Multiple tumours were always
undetected and large tumours were often overlooked. CONCLUSIONS: Despite
its continuing popularity, IVU is a poor means of identifying bladder
tumours and routine views of the full bladder should be abandoned.
7
UI - 11287448
AU - Castelao JE; Yuan JM; Skipper PL; Tannenbaum SR; Gago-Dominguez M;
TI -
Crowder JS; Ross RK; Yu MC
Gender- and smoking-related bladder cancer risk.
SO - J Natl Cancer Inst 2001 Apr 4;93(7):538-45
AD - University of Southern California/Norris Comprehensive Cancer Center,
Keck School of Medicine of the University of Southern California, Los
Angeles 90089-9181, USA. castelao@hsc.usc.edu
BACKGROUND: There is growing evidence that, when smoking habits are
comparable, women incur a higher risk of lung cancer than men. Because
smokers are also at risk for bladder cancer, we investigated possible
sex differences in the susceptibility to bladder cancer among smokers.
METHODS: A population-based, case--control study was conducted in Los
Angeles, CA, involving 1514 case patients with bladder cancer and 1514
individually matched population control subjects. Information on tobacco
use was collected through in-person interviews. Peripheral blood was
collected from study participants to measure 3- and 4-aminobiphenyl
(ABP)-hemoglobin adducts, a marker of arylamine exposure. Data were
analyzed to determine whether the risk of bladder cancer differs between
male and female smokers and whether female smokers exhibit higher levels
of ABP-hemoglobin adducts than male smokers with comparable smoking
habits. All statistical tests were two-sided. RESULTS: Cigarette smokers
had a statistically significant 2.5-fold higher risk (95% confidence
interval = 2.1 to 3.0) of bladder cancer than never smokers. Use of
filtered versus nonfiltered cigarettes, low-tar versus higher tar
cigarettes, or the pattern of inhalation did not modify the risk. The
risk of bladder cancer in women who smoked was statistically
significantly higher than that in men who smoked comparable numbers of
cigarettes (P =.016 for sex-lifetime smoking interaction). Consistent
with the sex difference in smoking-related bladder cancer risk, the
slopes of the linear regression lines of the 3- and 4-ABP--hemoglobin
adducts by cigarettes per day were statistically significantly steeper
in women than in men (P values for sex differences <.001 and.006,
respectively). CONCLUSION: The risk of bladder cancer may be higher in
women than in men who smoked comparable amounts of cigarettes.
8
UI - 12050554
AU - van der Poel HG; Molenaar B; van Beusechem VW; Haisma HJ; Rodriguez R;
TI -
Curiel DT; Gerritsen WR
Epidermal growth factor receptor targeting of replication competent
adenovirus enhances cytotoxicity in bladder cancer.
SO - J Urol 2002 Jul;168(1):266-72
AD - Department of Urology, The Netherlands Cancer Institute, Amsterdam, The
Netherlands.
PURPOSE: We evaluated the delivery and oncolytic potential of targeted
replication competent adenoviruses in bladder cancer lines. MATERIALS
AND METHODS: Seven established human bladder cancer tumor lines (5637,
SW800, TCCsup, J82, Scaber, T24 and 253J) were studied for the
expression of integrins alpha(v)beta3, alpha(v)beta5, Coxsackievirus and
adenovirus receptor, epidermal growth factor receptor (EGF-R) and
epithelial cell adhesion molecule antigens using flow cytometry
analysis. Bispecific single chain Fv fragments were used to target
replication deficient luciferase reporter adenovirus to EGF-R (425-s11)
or to epithelial cell adhesion molecule (C28-s11) antigens. Moreover, a
fiber modified adenovirus targeting alpha(v)-integrins was studied.
Replication competent serotype-5 adenoviruses attenuated to replicate
specifically in retinoblastoma pRb (Ad5-d24) or p53 deficient (Ad5-d55K)
cells were tested in vitro for oncolytic properties. RESULTS: Low to
absent Coxsackievirus and adenovirus receptor expression was found in 5
of the 7 tumor lines (SW800, J82, T24, 5637 and Scaber). EGF-R
expression was found in all cell lines, whereas elevated epithelial cell
adhesion molecule expression was seen in 3 (5637, Scaber and TCCsup),
alpha(v)beta3-integrin was found in 1 (Scaber) and
alpha(v)beta5-integrin was found in 3 (TCCsup, 253J and T24). EGF-R
targeting using 425-s11 improved transgene expression in all cell lines
from 2.1 to 12.5 times over nontargeted viruses. Epithelial cell
adhesion molecule and integrin targeting was inferior to EGF-R targeting
with a maximal increase in transgene expression of 2 times for
epithelial cell adhesion molecule in 5637cells and 1.6 times for
integrin targeting in T24 cells. Comparison of the wild-type replication
competent virus with conditionally replicating adenoviruses (Ad5-d55K
and Ad5-d24) showed superior oncolytic activity for the latter 2 in all
lines. Furthermore, improved cytotoxicity (29% to 33%) was obtained in 4
of the 7 lines after pre-incubation of Ad5-d24 with 425-s11.
CONCLUSIONS: EGF-R directed bispecific single chain antibodies enhance
adenovirus mediated transgene expression and oncolysis in bladder cancer
lines.
9
UI - 12050493
AU - Yossepowitch O; Dalbagni G
TI -
Transitional cell carcinoma of the bladder in young adults:
presentation, natural history and outcome.
SO - J Urol 2002 Jul;168(1):61-6
AD - Department of Urology, Memorial Sloan-Kettering Cancer Center, New York,
New York, USA.
PURPOSE: The natural history and prognosis of bladder cancer in young
patients is not well defined. We analyzed our experience with such
patients. MATERIALS AND METHODS: The medical records of 74 patients
presenting with transitional cell carcinoma of the bladder at 40 years
and younger were reviewed and compared with those of 75 patients
diagnosed with bladder transitional cell carcinoma at 65 years old and
older. RESULTS: Median followup was 28.1 months (range 1 to 155) and
34.7 (range 1 to 178) in young and old patients, respectively. Initial
stage distribution was similar with 80% of patients presenting with
superficial disease. No difference was observed in the disease-free
progression or disease-free recurrence rate among the groups in patients
initially presenting with stage Ta, Tis or T1 tumors. A significantly
higher proportion of older versus younger patients underwent cystectomy
(54% versus 23%). We did not observe a difference in pathological stage
distribution or the rate of extravesical disease in young and old
patients (47% and 45%, respectively). Younger patients who ultimately
underwent radical cystectomy had significantly lower disease-free
survival, mainly due to a higher rate of distant metastases than in the
older group (41% versus 24%). The rate of local recurrence was similar.
CONCLUSIONS: Bladder transitional cell carcinoma in young adults has a
clinical stage distribution and natural history similar to that in older
patients. Our study suggests that a subset of young patients who
ultimately undergo radical cystectomy have particularly aggressive
tumors, portending a poor outcome.
10
UI - 12050494
AU - Filbeck T; Pichlmeier U; Knuechel R; Wieland WF; Roessler W
TI -
Clinically relevant improvement of recurrence-free survival with
5-aminolevulinic acid induced fluorescence diagnosis in patients with
superficial bladder tumors.
SO - J Urol 2002 Jul;168(1):67-71
AD - Department of Urology, St. Joseph's Hospital and Institute of Pathology,
University of Regensburg, Germany.
PURPOSES: Fluorescence diagnosis induced by 5-aminolevulinic acid
enables more thorough transurethral resection of superficial bladder
carcinoma compared with conventional white light. We performed a
prospective, single institution, randomized trial to investigate whether
the residual tumor rate and long-term tumor recurrence can be decreased
by fluorescence diagnosis. MATERIALS AND METHODS: A total of 301
patients underwent transurethral resection of bladder tumors with white
light or fluorescence diagnosis. Transurethral resection was repeated 5
to 6 weeks later to evaluate the residual tumor rate. To determine
recurrence-free survival patient followup was performed every 3 months
by white light cystoscopy and urine cytology. Recurrence-free survival
was analyzed via Kaplan-Meier methods and multivariable Cox regression
analysis. RESULTS: A total of 191 patients with superficial bladder
carcinoma were available for efficacy analysis. The residual tumor rate
was 25.2% in the white light arm versus 4.5% in the fluorescence
diagnosis arm (p <0.0001). Median followup in the white light arm in 103
cases was 21.2 months (range 4 to 40) compared with 20.5 (range 3 to 40)
in the 88 in the fluorescence diagnosis arm. Recurrence-free survival in
the fluorescence diagnosis group was 89.6% after 12 and 24 months
compared with 73.8% and 65.9%, respectively, in the white light group (p
= 0.004). This superiority proved to be independent of risk group. The
adjusted hazard ratio of fluorescence diagnosis versus white light
transurethral resection was 0.33 (95% confidence interval 0.16 to 0.67).
CONCLUSIONS: Fluorescence diagnosis is significantly superior to
conventional white light transurethral resection with respect to the
residual tumor rate and recurrence-free survival. The differences in
recurrence-free survival imply that fluorescence diagnosis is a
clinically relevant procedure for decreasing the number of tumor
recurrences.
11
UI - 11482447
AU - Kontani K; Kawakami M; Nakajima T; Katsuyama T
TI -
Tobacco use and occupational exposure to carcinogens, but not
N-acetyltransferase 2 genotypes are major risk factors for bladder
cancer in the Japanese.
SO - Urol Res 2001 Jun;29(3):199-204
AD - Department of Urology, Shinshu University School of Medicine, Matsumoto,
Japan.
Our study investigated the risks of genotypes of N-acetyltransferase 2
(NAT2), tobacco use and/or occupational exposure to carcinogens in
patients with bladder cancer and in age- and sex-matched controls in
Japanese. NAT2 genotypes were categorized into two groups, homozygous
mutant (slow acetylator genotype) and homozygous and heterozygous wild
type (fast acetylator genotype). The percentage of NAT2 slow acetylator
types was 6.7% in the bladder cancer patients, close to the value for
controls (6.1%). There was no association between NAT2 slow acetylator
genotype and the risk of bladder cancer. This association was also
insignificant when subjects were restricted to those who used tobacco or
those occupationally exposed to carcinogens. In contrast, tobacco use in
combination with exposure to carcinogens was a significant risk factor,
as based on the odds ratio and chi-square test. The combination of both
factors should be an additive risk factor for bladder cancer. In this
study, we demonstrated that the environmental factors of smoking habit
and occupational exposure for carcinogenicity are much more important
than genetic factors in bladder cancer.
12
UI - 11528193
AU - Sagol O; Yorukoglu K; Tuna B; Ozer E; Sis B; Guray M; Mungan U; Kirkali
TI -
Z
Expression of pS2 protein and its relation with the Ki-67 proliferative
indices and tumor recurrence in superficial bladder carcinomas.
SO - Eur Urol 2001 Aug;40(2):163-8
AD - Department of Pathology, Dokuz Eylul University School of Medicine,
Inciralti/Izmir, Turkey.
OBJECTIVE: To investigate the expression and possible role of pS2
protein as a predictor of tumor recurrence in superficial transitional
cell carcinoma of the bladder and to determine its relation with tumor
stage, grade, size, number, recurrence and proliferative activity.
METHODS: Paraffin sections of transurethral resection material from 80
patients with superficial transitional cell bladder carcinoma were
stained with pS2 and Ki-67 antibodies using the standard streptavidin
biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a
scale of 1-3 and the Ki-67-labelling index was determined as a
percentage of positively staining tumor cells. RESULTS: An inverse
relationship was found between pS2 expression and Ki-67 index (p<0.001).
pS2 expression showed no relation with any clinicopathological
prognostic parameters as well as the recurrence rate. The recurrence
rate was only associated with increased tumor number (p = 0.05), while
the time to first recurrence was significantly related to tumor size,
proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03,
respectively). On the other hand, higher tumor grade was correlated with
increased tumor number, Ki-67 index and tumor stage (p = 0.016, p =
0.006, and p<0.001, respectively). CONCLUSION: pS2 expression is
associated with a low proliferative potential of superficial
transitional cell carcinoma of the bladder, while it does not seem to be
related to the recurrence rate of the tumor and other prognostic
factors. Tumor size and proliferative activity may aid in the estimation
of the time to the first recurrence.
13
UI - 11684850
AU - Popov I; Jelic S; Radosavljevic D; Nikolic-Tomasevic Z
TI -
Amsacrine and cisplatin in poor prognosis patients with metastatic
transitional cell carcinoma of the urothelium: a phase-II study.
SO - Eur Urol 2001 Sep;40(3):324-9
AD - Institute of Oncology and Radiology of Serbia, Belgrade, FR Yugoslavia.
ipopov@ncrc.ac.yu
OBJECTIVES: Amsacrine, as a single agent, was reported to be effective
in patients with metastatic transitional cell carcinoma of the urinary
bladder. Amsacrine is also associated with a lower toxicity than
cyclophosphamide, doxorubicin and cisplatin therapy and has similar
activity. But amsacrine has been forgotten in clinical studies of
transitional cell carcinoma of the urinary bladder. The aim of present
study was to investigate the toxicity and efficacy of amsacrine and
cisplatin in chemotherapy-naive patients with metastatic transitional
cell carcinoma of the urinary bladder. METHODS: We have treated 54
patients (41 males/13 females) with a median age of 62 (38-72) years.
Performance status was 0/2, I/27 II/17 and III/8. The treatment
included: amsacrine 85 mg/ m(2), days 1-2, and cisplatin 30 mg/m(2),
days 2-5. Cycles were repeated every 4 weeks. We applied 169 cycles
(median 3/patient). Of 54 patients, 39 had previous surgery and 12 had
previous radiotherapy. Histological tumor grade was I/7, II/27 and
III/20. RESULTS: 51 patients were evaluable for response (3 patients
refused further treatment during the first cycle): 2 complete remission
(4%); 15 partial remission (29%); 23 stable disease (45%), and 11
progressive disease (22%). The response rate was 33% (95% CI 21-46). On
an intent-to-treat basis the response was 32% (95% CI 19-44). Durations
of complete and partial responses were 14 (range 12-16) and 6.5 (range
3-11) months, respectively. Median survival was 9 (range 3-21) months.
All patients were evaluable for toxicity. Grades III-IV toxicity was as
follows: anemia 11%; neutropenia 37%, and thrombocytopenia 20%. None of
the patients was excluded from the study because of toxicity.
CONCLUSION: The combination of amsacrine and cisplatin is a regimen with
mild and manageable toxicity. The present regimen seems to be active.
Randomized study of the present regimen versus another low-toxicity
regimens are necessary, especially for poor prognosis patients including
those with a low performance status.
14
UI - 11711760
AU - Balbi JC; Larrinaga MT; De Stefani E; Mendilaharsu M; Ronco AL; Boffetta
TI -
P; Brennan P
Foods and risk of bladder cancer: a case-control study in Uruguay.
SO - Eur J Cancer Prev 2001 Oct;10(5):453-8
AD - Seccion de Epidemiologia, Instituto Nacional de Oncologia, Montevideo,
Uruguay.
A case-control study on 144 cases of transitional cell bladder carcinoma
and 576 hospitalized controls was conducted in Montevideo, Uruguay.
Barbecued meat, salted meat and fried eggs were associated with
significant increased risks of bladder cancer (odds ratio (OR) for high
intake of salted meat 4.04, 95% confidence interval (CI) 2.24-7.27). On
the other hand, all fruits, cooked vegetables, potatoes and cheese were
associated with inverse associations (OR for high consumption of
potatoes 0.38, 95% CI 0.23-0.64). The associations with salted and
barbecued meat suggest that the way of preserving or cooking meat play a
role in bladder carcinogenesis. More precisely, N-nitroso compounds and
heterocyclic amines could be involved in this process.
15
UI - 12036941
AU - Thompson TE; Rogan PK; Risinger JI; Taylor JA
TI -
Splice variants but not mutations of DNA polymerase beta are common in
bladder cancer.
SO - Cancer Res 2002 Jun 1;62(11):3251-6
AD - Molecular and Genetic Epidemiology Group, The Laboratory of Molecular
Carcinogenesis, The National Institute of Environmental Health Sciences,
Research Triangle Park, NC 27709, USA.
DNA polymerase beta (POLbeta) is a highly conserved protein that
functions in base excision repair. Loss of the POLbeta locus on
chromosome 8p is a frequent event in bladder cancer, and loss of POLbeta
function could hinder DNA repair leading to a mutator phenotype. Both
point mutations and large intragenic deletions of POLbeta have been
reported from analysis of various tumor cDNAs but not from genomic DNA.
We noticed that the breakpoints of the presumed rearrangements were
delineated by exon-exon junctions, which could instead be consistent
with alternative splicing of POLbeta mRNA. We tested the hypothesis that
the reported intragenic deletion were splice variants by screening
genomic DNA of human bladder tumors, bladder cancer cell lines, and
normal bladder tissues for mutations or deletions in exons 1-14, exon
alpha, and the promoter region of POLbeta. We found no evidence of
somatic mutations or deletions in our sample set, although two
polymorphisms were identified. Examination of cDNA from a subset of the
original sample set revealed that truncated forms of POLbeta were
surprisingly common. Forty-eight of 89 (54%) sequenced cDNA clones had
large deletions, each beginning and/or ending exactly at exon-exon
junctions. Because these deletions occur at exon-exon junctions and are
seen in cDNA but not genomic DNA, they are consistent with alternative
mRNA splicing. We describe 12 different splicing events occurring in 18
different combinations. Loss of exon 2 was the most frequent, being
found in 42 of 49 (86%) of the variant sequenced clones. The splice
variants appear to be somewhat more common and variable in bladder
cancer cell lines and tumor tissues but occur at a high frequency in
normal bladder tissues as well. We examine alternative splicing in terms
of the information content of splice donor and acceptor site sequences,
and discuss possible explanations for the predominant splicing event,
the loss of exon 2.
16
UI - 12057106
AU - Dreicer R
TI -
Locally advanced and metastatic bladder cancer.
SO - Curr Treat Options Oncol 2001 Oct;2(5):431-6
AD - Department of Hematology/Oncology, Taussig Cancer Center, Cleveland
Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
dreicer@ccf.org
Metastatic transitional cell carcinoma of the bladder is an aggressive
neoplasm characterized by rapid growth and dissemination with a median
survival of typically less than 1 year. Despite the availability of a
myriad of antineoplastics with moderate-significant anti-tumor activity
yielding overall response rates in the 40% to 80% range, randomized
trials continue to demonstrate median survival rates in the 13-
to14-month range, with very limited long-term survival. Subsets of
patients with advanced bladder cancer present additional management
problems, including those with renal insufficiency or
nontransitional-cell histology. Various observers have noted the
similarity in treatment outcomes in advanced bladder cancer and
extensive small cell lung cancer where chemotherapy produces relatively
high response rates but with limited impact on survival. The optimal
chemotherapy combination for patients with advanced bladder cancer
remains undefined, however, there is increasing recognition that in
order to achieve tangible improvements in complete response rates and
survival in this disease will likely require a combination of
chemotherapy and targeted molecular therapies and in some settings
adjunctive surgery.
17
UI - 11828990
AU - Gontero P; Tizzani A; Muir GH; Caldarera E; Macaluso MP
TI -
The genetic alterations in the oncogenic pathway of transitional cell
carcinoma of the bladder and its prognostic value.
SO - Urol Res 2001 Dec;29(6):377-87
AD - Patologia Urologica, Universita' di Torino, Italy. pgontero@hotmail.com
This review focuses on the main oncogenes studied in transitional cell
carcinoma (TCC) in order to describe their mechanisms of action and
investigate their possible prognostic value. Each oncogene family is
reported following the order through which the proliferative signal is
transduced from the extracellular space via a growth factor to the
nucleus where transcription factors are switched on. Oncogenic
activation at any level of the pathway will cause an increased
transcription of genes enhancing the cell cycle, and proliferation will
therefore be amplified. The main molecular or immunohistochemical
studies from the literature on the aberrant expression of these genes
are examined and compared with the aid of tables. Conclusions suggest
that, although some may initially appear promising, no oncogene, has
thus far been found to have a definite prognostic value superior to
conventional grading and staging.
18
UI - 11828992
AU - Toruner GA; Ucar A; Tez M; Cetinkaya M; Ozen H; Ozcelik T
TI -
P53 codon 72 polymorphism in bladder cancer--no evidence of association
with increased risk or invasiveness.
SO - Urol Res 2001 Dec;29(6):393-5
AD - Department of Molecular Biology and Genetics, Bilkent University,
Ankara, Turkey.
We studied the effect of the p53 gene Arg72Pro polymorphism on bladder
cancer susceptibility in a case control study of 121 bladder cancer
patients and 114 age-sex matched controls to determine whether this
polymorphism is a biomarker for the risk and how aggressive the disease
is. Genomic DNA was obtained from venous blood samples for genotype
determination by PCR and restriction digestion. The genotype frequencies
in the patient group were Arg/Arg: 0.3553, Arg/Pro: 0.4711, Pro/Pro:
0.1736, and in the control group Arg/Arg: 0.3684, Arg/Pro: 0.4825,
Pro/Pro: 0.1491. The distribution of genotypes between the two groups
was not statistically different (chi2 = 0.260, df: 2, P=0.878). The
patient group was subdivided into two groups as superficial bladder
cancer (n = 88) and invasive bladder cancer (n = 33), according to the
presence of muscle invasion. The distribution of genotypes in the
superficial group was Arg/Arg: 0.3409, Arg/Pro: 0.5114, Pro/Pro: 0.1477
and in the invasive group Arg/Arg: 0.3940, Arg/Pro: 0.3636, Pro/Pro:
0.2424. No association was observed with the invasiveness of the tumor
(chi2 = 2.542, df 2, P = 0.281). Stratification of the data by tobacco
exposure did not result in a significant difference in genotype
frequencies. These data do not support an association between the p53
Arg72Pro polymorphism and bladder cancer.
19
UI - 11828995
AU - Tsai FJ; Lu HF; Yeh LS; Hsu CD; Chen WC
TI -
Lack of evidence for the association of tumor necrosis factor-alpha gene
promoter polymorphism with calcium oxalate stone and bladder cancer
patients.
SO - Urol Res 2001 Dec;29(6):412-6
AD - Department of Medical Genetics, China Medical College Hospital, China
Medical College, Taichung, Taiwan.
Urinary stone disease and bladder cancer are two of the most commonly
seen urologic diseases in Taiwan. Tumor necrosis factor-alpha
(TNF-alpha) is one of the cytokines secreted by macrophages and is
related to a sequence of events in response to inflammation and cancer
formation. We investigated the polymorphism of the TNF-alpha gene
promoter -308 as a genetic marker in searching for the association
between these two commonly seen urologic diseases. One hundred and
fourteen patients with transitional cell carcinoma of the urinary
bladder and 103 patients with calcium oxalate stone were compared with
150 healthy controls. The polymorphism was detected by polymerase chain
reaction-based restriction analysis (Nco I endonuclease). The results
revealed no significant differences between normal individuals and the
patients with the two commonly seen urologic diseases (P > 0.05). We
concluded that the polymorphism of the TNF-alpha promoter -308 is not a
valid genetic marker for these two urologic diseases.
20
UI - 11961481
AU - Wax JR; Pinette MG; Blackstone J; Cartin A; McCrann DJ
TI -
Nonbilharzial bladder carcinoma complicating pregnancy: review of the
literature.
SO - Obstet Gynecol Surv 2002 Apr;57(4):236-44
AD - Maine Medical Center, Portland, Maine, USA. waxj@mmc.org
The purpose of this review is to evaluate tumor presentation and
characteristics, and maternal-fetal outcomes of pregnancies complicated
by nonbilharzial bladder carcinoma. The mean age of the patients was
29.5 years (range = 18-40). Symptoms and diagnosis occurred after the
first trimester in 20 (83%) and 22 (92%) cases, respectively. Presenting
complaints included painless gross hematuria [N = 12 (50%)], vaginal
bleeding [N = 7 (29%)], dysuria [N = 2 (8.4%)], abdominal pain [N = 2
(8.4%)], and 1 instance each of urgency, frequency, recurrent cystitis,
and no symptoms. Tumors were initially identified by ultrasound [N = 12
(50%)], cystoscopy [N = 11 (46%)], and intravenous urography [N = 1
(4.5%)]. Transitional cell carcinoma was found in 17 (74%),
adenocarcinoma in 5 (22%), and squamous cell carcinoma in 1 (4.5%)
patient. Tumors did not favor a specific bladder location, tended to be
low grade [8 (40%) = grade 1, 7 (35%) = grade 2; 5 (21%) = grade 3], and
noninvasive [N = 19 (79%)]. Treatment was typically by transurethral
resection (N = 18), but 3 women required radical cystectomy, 2 received
radiation, 1 received chemotherapy, and 1 underwent partial cystectomy.
Three (14%) women died of their disease and 3 (14%) fetuses were lost
because of complications of cancer or its treatment. Bladder carcinoma
in pregnancy can mimic cystitis or obstetric hemorrhage and should be
considered when evaluations for these conditions are negative. Routine
ultrasound evaluation of the bladder in these patients may improve the
diagnostic yield. Pregnancy is not a contraindication to treating most
forms of bladder cancer. TARGET AUDIENCE: Obstetricians and
Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion
of this article, the reader will be able to list the various types of
bladder cancers, to describe the presenting symptoms in a patient with a
bladder cancer, and to outline the work up and treatment strategies for
bladder cancer.
21
UI - 11718635
AU - Xiaoxu L; Jianhong L; Jinfeng W; Klotz LH
TI -
Bladder adenocarcinoma: 31 reported cases.
SO - Can J Urol 2001 Oct;8(5):1380-3
AD - Department of Urology, The Second Affiliated Hospital of Shanxi Medical
University, Taiyuan, 030001 Shanxi, P.R. of China.
SUMMARY: retrospective review of 31 cases of bladder adenocarcinoma.
METHODS: All patients diagnosed with adenocarcinoma of the bladder at
the second affiliated hospital and commercial worker's hospital in
Shanxi between 1985 and 1999 were reviewed. RESULTS: The cohort
consisted of 31 patients, 25 with primary bladder adenocarcinoma, and 6
patients with urachal adenocarcinoma. Compared to the patients with
primary adenocarcinoma, the urachal group were younger (67 versus 56
years), and more likely to be female (M:F 3:1 versus 1:2), and had a
worse survival (45% versus 20% at 3 years). In the primary bladder
adenocarcinoma group, the 3-year survival rate was 45% after radical
cystectomy, and 33% after partial cystectomy. Local tumor recurrence
after partial cystectomy was 25%. CONCLUSION: Urachal adenocarcinoma
occurred in a younger age group with a female predominance compared to
primary adenocarcinoma. Partial cystectomy was associated with a
relatively high rate of local tumor recurrence.
22
UI - 12087158
AU - Gu L; Wu J; Zhu BB; Li GM
TI -
Deficiency of a novel mismatch repair activity in a bladder tumor cell
line.
SO - Nucleic Acids Res 2002 Jul 1;30(13):2758-63
AD - Department of Pathology and Laboratory Medicine, Suite MS 117, Markey
Cancer Center, University of Kentucky Medical Center, Lexington, KY
40536, USA.
We demonstrate here that a cell line derived from a bladder cancer is
defective in strand-specific mismatch repair. The mismatch repair
deficiency in this cell line is associated with microsatellite
instability and blocks an early step in the repair pathway. Since the
addition of a known mismatch repair component hMutSalpha, hMutSbeta,
hMutLalpha, replication protein A or proliferating cellular nuclear
antigen could not restore mismatch repair to the mutant extract, the
bladder tumor cell line is likely to be defective in an uncharacterized
repair component. However, the repair in the mutant extract could be
complemented by a partially purified activity derived from HeLa nuclear
extracts. Therefore, in addition to revealing that a loss of mismatch
repair function is associated with bladder cancer, this study provides
information implicating a new mismatch repair activity.
23
UI - 12123249
AU - Yamamoto S
TI -
Bladder cancer incidence in the world.
SO - Jpn J Clin Oncol 2002 Jun;32(6):224
24
UI - 12115522
AU - van Gils CH; Conway K; Li Y; Taylor JA
TI -
HRAS1 variable number of tandem repeats polymorphism and risk of bladder
cancer.
SO - Int J Cancer 2002 Aug 1;100(4):414-8
AD - Molecular and Genetic Epidemiology Section, Laboratory of Molecular
Carcinogenesis, National Institute of Environmental Health Sciences,
National Institutes of Health, Research Triangle Park, NC 27709, USA.
The HRAS1 variable number of tandem repeats (VNTR) polymorphism, 1 kb
downstream from the HRAS1 gene, has been reported to be associated with
risk of various cancers. To examine whether individuals with rare HRAS1
VNTR alleles are at increased risk of bladder cancer we carried out a
case control study with 230 bladder cancer cases and 203 hospital-based
controls frequency-matched on ethnicity, gender and age. For genotyping
we used a PCR-based long-gel electrophoretic assay that provides precise
allele size discrimination. We did not find evidence of a strong overall
effect of the HRAS1 VNTR on bladder cancer risk. Genotype data for
whites and blacks were analyzed separately, but the number of black
subjects was too small to estimate meaningful odds ratios. Compared to
white subjects with 2 common alleles, the odds ratio (OR) for white
subjects with 1 rare allele was 0.9 (95% confidence interval (CI) =
0.5-1.4) and for those with 2 rare alleles OR = 1.7 (95% CI = 0.6-5.4).
HRAS1 genotype may be related to the prognosis of bladder cancer,
however, because incident cases, i.e., newly diagnosed cases had a
higher frequency of rare alleles than did prevalent cases, i.e., cases
already existing at the time of recruitment. Repeating the analyses with
incident cases only (n = 53), the OR for subjects with 1 rare allele was
1.2 (95% CI = 0.6-2.4) and for those with 2 rare alleles 3.2 (95% CI =
0.8-13.7). The number of incident cases was too small to draw firm
conclusions on a possible association with a subgroup of tumors with a
poor prognosis. Published 2002 Wiley-Liss, Inc.
25
UI - 11906253
AU - Benimetskaya L; Guzzo-Pernell N; Liu ST; Lai JC; Miller P; Stein CA
TI -
Protamine-fragment peptides fused to an SV40 nuclear localization signal
deliver oligonucleotides that produce antisense effects in prostate and
bladder carcinoma cells.
SO - Bioconjug Chem 2002 Mar-Apr;13(2):177-87
AD - Howard Florey Institute of Experimental Physiology and Medicine,
University of Melbourne, Parkville, Victoria, 3052, Australia.
The development of antisense technology has focused on improving methods
for oligonucleotide delivery into cells. In the present work, we
describe a novel strategy for oligonucleotide delivery based on a
bifunctional peptide composed of a C-terminal protamine-fragment that
contains a DNA-binding domain and an N-terminal nuclear localization
signal sequence derived from the SV40 large-T antigen (The sequences of
two of the peptides are R6WGR6-PKKKRKV [s-protamine-NLS] and
R4SR6FGR6VWR4-PKKKRKV [l-protamine-NLS]). We demonstrated, by intrinsic
fluorescence quenching, that peptides of this class form complexes with
oligodeoxynucleotides. To evaluate delivery, we used a 20-mer
phosphorothioate oligomer (Isis 3521) targeted to the 3'-untranslated
region of the PKC-alpha mRNA and G3139, an 18-mer phosphorothioate
targeted to the first six codons of the human bcl-2 open reading frame,
and complexed them with either of two peptides (s- or l-protamine-NLS).
These peptides bind to and deliver antisense oligonucleotides to the
nucleus of T24 bladder and PC3 prostate cancer cells, as demonstrated by
confocal microscopy. Furthermore, as shown by Western and Northern
blotting, the peptide-oligonucleotide complexes produced excellent
downregulation of the expression of the complementary mRNAs, which in
turn resulted in downregulation of protein expression. However, under
certain circumstances (predominantly in PC3 cells), incubation of the
cells with chloroquine was required to produce antisense activity. Using
this strategy, PKC-alpha protein and mRNA expression in T24 and PC3
cells and bcl-2 expression in PC3 cells was reduced by approximately 75
+/- 10% at a minimum concentration of oligomer of 0.25 microM, in
combination with 12-15 microM peptide. On the basis of our results, we
conclude that arginine-rich peptides of this class may be potentially
useful delivery vehicles for the cellular delivery of antisense
oligonucleotides. This new strategy may have several advantages over
other methods of oligonucleotide delivery and may complement already
existing lipid-based technologies.
26
UI - 12094376
AU - Swierczynski SL; Epstein JI
TI -
Prognostic significance of atypical papillary urothelial hyperplasia.
SO - Hum Pathol 2002 May;33(5):512-7
AD - Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD
21231, USA.
Typical papillary hyperplasia, a recently recognized precursor lesion to
low-grade papillary urothelial neoplasms, consists of undulating folds
of cytologically benign urothelium. Well-developed, branching
fibrovascular cores of a papillary neoplasm are not evident. We have
noted lesions with the architectural pattern of papillary hyperplasia;
however, the overlying urothelium demonstrated varying degrees of
cytologic atypia. We identified 15 cases of atypical papillary
hyperplasia (13 males, 2 females, age 55 to 92) with overlying
urothelium showing cytologic atypia. Of these cases, 8 (53%) were
received in consultation. Of the 15 cases, 8 exhibited overlying flat
carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were
transitional between papillary hyperplasia with atypia and the earliest
lesions of papillary neoplasia. Of these cases, 5 patients had multiple
specimens with atypical papillary hyperplasia (range, 2 to 8) over time.
Concurrent to the diagnosis of atypical papillary hyperplasia, there
were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1),
papillary neoplasm of low malignant potential with CIS (n = 1),
high-grade papillary urothelial carcinoma (n = 10; 3 with CIS),
small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n =
1). Of 11 patients with known prior history, 2 had 12 prior urothelial
neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial
neoplasms of low malignant potential, and 1 high-grade papillary
cancer). Of 10 patients with atypical papillary hyperplasia and a
minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4),
papilloma (n = 1), papillary neoplasm of low malignant potential (n =
1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and
high-grade pap
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