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NCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Bladder Cancer - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
UI - 11825664
AU - Lee SJ; Cho SH; Park SK; Kim SW; Park MS; Choi HY; Choi JY; Lee SY; Im
TI -
HJ; Kim JY; Yoon KJ; Choi H; Shin SG; Park TW; Rothman N; Hirvonen A;
Kang D
Combined effect of glutathione S-transferase M1 and T1 genotypes on
bladder cancer risk.
SO - Cancer Lett 2002 Mar 28;177(2):173-9
AD - Department of Internal Medicine, Hallym University College of Medicine,
ChoonChun, South Korea.
To evaluate the association between genetic polymorphism of GSTM1, GSTT1
and development of bladder cancer, a hospital-based case-control study
was conducted in South Korea. The study population consisted of 232
histologically confirmed male bladder cancer cases and 165 male controls
enrolled from urology departments with no previous history of cancer or
systemic diseases in Seoul during 1997-1999. The GSTM1 null genotype was
significantly associated with bladder cancer (OR: 1.6, 95% CI: 1.0-2.4),
whereas the association observed for GSTT1 null genotype did not reach
statistical significance (OR: 1.3, 95% CI: 0.9-2.0). There was a
statistically significant multiple interaction between GSTM1 and GSTT1
genotype for risk of bladder cancer (P=0.04); the risk associated with
the concurrent lack of both of the genes (OR: 2.2, 95% CI: 1.2-4.3) was
greater than the product of risk in men with GSTM1 null/GSTT1 present
(OR: 1.3, 95% CI: 0.7-2.5) or GSTM1 present/GSTT1 null (OR: 1.1, 95% CI:
0.6-2.2) genotype combinations.
2
UI - 11971182
AU - Simon R; Struckmann K; Schraml P; Wagner U; Forster T; Moch H; Fijan A;
TI -
Bruderer J; Wilber K; Mihatsch MJ; Gasser T; Sauter G
Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary
bladder cancer.
SO - Oncogene 2002 Apr 11;21(16):2476-83
AD - Institute for Pathology and Urologic Clinics, University of Basel,
Schoenbeinstrasse 40, CH-4003 Basel, Switzerland.
The chromosomal region 12q13-q15 is recurrently amplified in bladder
cancer. Putative target genes located in this region include MDM2, CDK4,
and GLI. To evaluate the involvement of these genes in bladder cancer,
we screened a tissue microarray (TMA) containing 2317 samples by
fluorescence in situ hybridization (FISH). Amplification was found for
MDM2 in 5.1%, for CDK4 in 1.1%, and for GLI in 0.4% of interpretable
tumors. Among tumors having amplification of at least one of these
12q13-q15 genes, 76.6% had amplification of MDM2 alone and 6.4% had
amplification of CDK4 alone. Coamplifications were seen of MDM2 and CDK4
in 10.6%, and of CDK4 and GLI in 6.4%. Neither coamplifications of all
three genes nor isolated GLI amplifications were found. These data
suggest a prominent role of MDM2 as a 12q13-q15 amplification target in
bladder cancer. However, independent CDK4 amplifications do also occur
suggesting either two non-overlapping amplification sites or else a
minimal overlapping region between MDM2 and CDK4 perhaps containing
another yet unknown oncogene. The frequency of amplification increased
significantly from stage pTa to pT1-4 (P<0.04) and from low to high
grade (P<0.005). These data are consistent with a high level of genetic
instability in invasively growing and high-grade bladder tumors.
3
UI - 11820413
AU - Raitanen MP; Aine R; Kylmala T; Kallio J; Liukkonen T; Tammela T; The
TI -
Finnbladder Group
The dilemma of suspicious urine cytology in patients being followed for
bladder cancer.
SO - Ann Chir Gynaecol 2001;90(4):256-9
AD - Division of Urology, Tampere University Hospital, Finland.
mika.raitanen@epshp.fi
BACKGROUND AND AIMS: Urine cytology is gold standard for clinical tests
used in the diagnosis and follow-up of bladder cancer. Cytology,
however, exhibits variable sensitivity depending on tumour grade and
interpretation of urine specimens is highly dependent on the skill of
the examiner. Furthermore, a "suspicious" cytology report (class III)
makes clinicians uncomfortable. In these cases, a more objective test,
such as the BTA stat Test, may be useful in providing clarification. The
aim of this study was to evaluate the dilemma of suspicious routine
urine cytology and to determine whether the BTA stat Test provides
diagnostic aid in this rare but controversial category. MATERIAL AND
METHODS: 506 consecutive patients who were being followed for bladder
cancer were included in the study. A voided urine sample was obtained
prior to routine follow-up cystoscopy and split for culture and testing
with the BTA stat Test. Clinical status of the disease was evaluated in
patients with suspicious urine cytology, and the diagnostic aid of the
BTA stat Test in these patients was determined. RESULTS: A total of 57
patients (11.3%) had urine cytology classified as suspicious. The BTA
stat Test was positive in 29 (50.9%) and negative in 28 (49.1%)
patients. Nineteen (33.3%) patients had recurrence at routine
cystoscopy. Of the remaining 38 patients, 10 were further investigated
due to a positive BTA stat Test. Two additional recurrences were
detected bringing the total number of recurrences to 21 (36.8%), 48.3%
(14/29) of the patients with positive and 25.0% (7/28) of the patients
with negative BTA stat Test had recurrence (p = 0.069). Overall, 65.5%
(19/29) of the patients with a positive BTA stat Test were found to have
recurrence either at routine cystoscopy, at further investigations, or
at the next cystoscopy compared to that of 35.7% (19/28) in those with
negative testing (p = 0.024). The overall sensitivity of the BTA stat
Test was 66.7%, and the specificity was 58.3%. CONCLUSIONS: At least a
third of the patients under follow-up for bladder cancer with suspicious
cytology had a recurrence, indicating that these patients are a risk
group for recurrence. More importantly, a BTA stat Test result seems to
provide some help in distinguishing those patients with very high risk
for recurrence, for whom invasive further investigations should be
conducted and a close follow-up policy maintained.
4
UI - 11820414
AU - Raitanen MP; Leppilahti M; Tuhkanen K; Forssel T; Nylund P; Tammela T;
TI -
The FinnBladder Group
Routine follow-up cystoscopy in detection of recurrence in patients
being monitored for bladder cancer.
SO - Ann Chir Gynaecol 2001;90(4):261-5
AD - Department of Urology, Tampere University Hospital, Finland.
mika.raitanen@epshp.fi
BACKGROUND AND AIMS: Cystoscopy and urine cytology are the standard
tools for monitoring superficial bladder cancer. The sensitivity of
cystoscopy is, however, limited to the tumours that can be visualised,
and the sensitivity of cytology is relatively low in low-stage/low-grade
tumours. Therefore, new tumour markers have been developed. BTA stat has
been reported to have high sensitivity in detecting both primary and
recurrent bladder tumours, and may have the potential to detect tumours
that cannot be visualised by routine cystoscopy including recurrences in
upper tract. The objective of the study was to analyse the reliability
of routine follow-up cystoscopy by further investigating patients with
positive marker status, BTA stat Test and urine cytology, but negative
cystoscopy. MATERIAL AND METHODS: 446 consecutive patients being
followed for bladder cancer were analysed in a prospective multicenter
study. A voided urine sample was obtained prior to cystoscopy and split
for culture, cytology and BTA stat testing. In the case of positive
marker status, BTA stat Test or urine cytology, but negative cystoscopy
patients were further investigated by i.v. urography or renal ultrasound
and random biopsies. The sensitivity of routine follow-up cystoscopy is
reported. RESULTS: Of 446 patients 131 (29.4%) had a bladder cancer
recurrence at routine cystoscopy. Of the remaining 315 patients not
having recurrent tumour at cystoscopy, 56 patients (17.8%) had positive
BTA stat Test result, 6 (1.9%) had positive cytology and 5 were positive
by both tests. Nine recurrences that were missed at routine follow-up
cystoscopy were detected by further investigations making the total
number of bladder confined recurrent tumours 140 (140/446, 31.4%). Five
of these 9 recurrences were high grade lesions (1 T1G3, 4 CIS), of which
4 were detected by positive cytology. The overall sensitivity of
cystoscopy was 93.6%. CONCLUSIONS: We found that routine follow-up
cystoscopy may miss over five percent of the recurrent tumours. Although
cystoscopy remains the gold standard for bladder cancer follow-up, it is
suggested that even with negative cystoscopy patients with positive
marker status, BTA stat Test and especially urine cytology, should be
considered at risk for coexisting, and in some case even high grade
recurrence.
5
UI - 11859200
AU - Martin SA; Sears DL; Sebo TJ; Lohse CM; Cheville JC
TI -
Smooth muscle neoplasms of the urinary bladder: a clinicopathologic
comparison of leiomyoma and leiomyosarcoma.
SO - Am J Surg Pathol 2002 Mar;26(3):292-300
AD - Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester,
Minnesota 55905, USA.
We report the clinicopathologic, immunohistochemical, and DNA ploidy
findings of 18 leiomyosarcomas of the urinary bladder. In addition, we
compare these malignant smooth muscle tumors with 10 cases of urinary
bladder leiomyoma. The 14 male and four female patients with
leiomyosarcoma ranged in age from 25 to 88 years (mean 64 years). The
tumors ranged from 3.0 to 15.0 cm (mean 7.1 cm) in greatest dimension
and were moderately to highly cellular, consisting of interlacing
fascicles of spindled cells with mild to marked nuclear atypia.
Coagulative tumor necrosis was identified in 14 cases (78%), and mitotic
activity ranged from 1 to 42 mitotic figures (MF) per 10 high power
fields (HPF) (mean 12 MF/10 HPF). Tumors were classified as either
high-grade (12 cases) or low-grade (six cases) based on nuclear atypia,
mitotic activity, and tumor necrosis. Actin positivity was present in 15
tumors (83%), and desmin immunoreactivity was present in seven tumors
(39%). All cases were negative for epithelial markers and S-100.
Proliferative activity, as assessed by MIB-1 staining, ranged from 0.1%
to 51.4% (median 9.1%). Seven (39%) of the leiomyosarcomas were DNA
aneuploid, eight (44%) were tetraploid, and three (17%) were diploid.
Five patients underwent radical cystoprostatectomy, one radical
cystectomy, seven had partial cystectomy, two underwent pelvic
exenteration, and three patients had transurethral resection only.
Follow-up information was available on all 18 cases and ranged from 2 to
68 months (mean 22 months). Of the 12 patients with high-grade tumors,
six (50%) died of disease from 2 to 20 months (mean 7 months) after
diagnosis and three patients (25%) are alive with metastatic tumor. Two
of the six patients with low-grade leiomyosarcoma died of tumor, 61 and
68 months after diagnosis. There were five male and five female patients
with leiomyoma ranging in age from 22 to 78 years (mean 61 years). The
tumors ranged from 0.5 to 4.5 cm (mean 1.6 cm) in greatest dimension,
were well circumscribed, and had low cellularity. Mitotic activity,
necrosis, and cellular atypia were absent, and the tumors were strongly
positive for both actin and desmin. MIB-1 staining ranged from 0% to
3.8% (median 0.8%). Seven (87.5%) of the leiomyomas were DNA diploid or
near-diploid and one (12.5%) was DNA aneuploid. Six patients were
treated with transurethral resection and four with partial cystectomy.
All 10 patients were alive at the last follow-up (mean follow-up 75
months), and no tumor recurred or metastasized. Our study shows that
low-grade leiomyosarcomas are capable of malignant behavior, and
high-grade leiomyosarcomas appear to behave more aggressively than
low-grade tumors. In addition, the diagnosis of urinary bladder
leiomyoma should be reserved for noninfiltrative smooth muscle tumors
lacking mitotic activity, cytologic atypia, and necrosis.
6
UI - 11920626
AU - Tada Y; Wada M; Migita T; Nagayama J; Hinoshita E; Mochida Y; Maehara Y;
TI -
Tsuneyoshi M; Kuwano M; Naito S
Increased expression of multidrug resistance-associated proteins in
bladder cancer during clinical course and drug resistance to
doxorubicin.
SO - Int J Cancer 2002 Apr 1;98(4):630-5
AD - Department of Medical Biochemistry, Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan.
Overexpression of the P-glycoprotein/multidrug resistance 1 (MDR1) and
multidrug resistance protein 1 (MRP1) gene is closely associated with
the clinical outcome of various malignancies, and it is involved in
responses to some anticancer chemotherapeutic agents including
doxorubicin. Six human MRP subfamily members (MRP2-7) with structural
similarities to MRP1 have been identified. Recently, the relationships
between MRP2 and MRP3 expression levels of some cancer cells and drug
sensitivity to doxorubicin have been reported, but the relationship
between the clinical samples and drug sensitivity remains unclear. We
determined the expressions of the MDR1, MRP1, MRP2 and MRP3 gene in
bladder cancer during the clinical course and sought to learn whether
the expression was correlated with drug responses to doxorubicin.
Doxorubicin, used in chemotherapeutic treatment including intravesical
and systemic chemotherapy, is an important anticancer agent for the
treatment of bladder cancer. We used quantitative reverse
transcriptase-polymerase chain reaction (RT-PCR) analysis for our study,
and the sensitivity to doxorubicin in bladder cancer was determined
using the in vitro succinate dehydrogenase inhibition test. Using 47
clinical samples of bladder cancer, we confirmed the significant
correlation of MDR1, MRP1 and MRP3 mRNA levels with resistance to
doxorubicin. We showed that the expression of MDR1, MRP1, MRP2 and MRP3
in recurrent tumors and residual tumors after chemotherapeutic treatment
was higher than that in untreated primary tumors. In particular, the
MDR1 expression in residual tumors was 5.7-fold higher than that in
untreated primary tumors. Copyright 2002 Wiley-Liss, Inc.
7
UI - 11959532
AU - Anonymous
TI -
Bladder cancer.
SO - Harv Mens Health Watch 2002 Apr;6(9):3-6
8
UI - 11872026
AU - Saad A; Hanbury DC; McNicholas TA; Boustead GB; Morgan S; Woodman AC
TI -
A study comparing various noninvasive methods of detecting bladder
cancer in urine.
SO - BJU Int 2002 Mar;89(4):369-73
AD - Department of Urology, Lister Hospital, Stevenage, UK.
adnansaad99_@hotmail.com
OBJECTIVES: To compare the nuclear matrix protein (NMP)-22 assay,
bladder tumour specific antigen (BTAstat) test, telomerase activity
(using the telomeric repeat amplification protocol assay, TRAP) and a
haemoglobin dipstick test for their ability to replace voided urine
cytology (VUC) for detecting bladder cancer. PATIENTS AND METHODS: The
study included 120 urological patients prospectively recruited and
assessed before surgery. A single freshly voided urine sample
(approximate 100 mL) was collected from each patient and aliquoted for
each test. All assays were conducted according to the manufactures'
guidelines; 79 patients were tested for telomerase activity. The results
were then compared with VUC and the diagnosis confirmed by cystoscopy
and histology. RESULTS: Fifty-two patients had histologically confirmed
transitional cell carcinoma. The overall sensitivity for BTAstat, NMP22,
telomerase, VUC and dipstick testing was 63%, 81%, 84%, 48% and 50%,
respectively. Combining the results for telomerase and NMP22 gave a
sensitivity of 100%. For G1 tumours the respective sensitivities were
23%, 62%, 56%, 23% and 15%, for G2 tumours, 68%, 86%, 92%, 50% and 41%
and for G3 tumours 88%, 88%, 100%, 71% and 82%. For pTa tumours the
respective detection rates were 48%, 70%, 84%, 39% and 30%, for pT1
tumours 80%, 90%, 90%, 50% and 50%, for pT2/pTis tumours, 100/100%,
100/100%, 100/100%, 88/100% and 88/83%. The overall specificity for the
respective tests was 82%, 87%, 93%, 87% and 54%; combining the results
of NMP22 and telomerase activity increased the specificity to 96%.
CONCLUSIONS: There was significantly better detection than VUC when
using the NMP22 and TRAP assay, especially for well-differentiated (P <
0.001 and 0.0027, respectively) and superficial tumours (P < 0.001 and
0.034, respectively). Combining the results of NMP22 and telomerase
activity yielded values comparable with cystoscopy.
9
UI - 11710636
AU - Helpap B
TI -
Nonepithelial neoplasms of the urinary bladder.
SO - Virchows Arch 2001 Oct;439(4):497-503
AD - Department of Pathology, Hegau-Klinikum Singen, University of Freiburg,
Germany. pathologie@hegau-klinikum.de
Nonepithelial tumors are rare in the urinary bladder, but their exact
classification is very important in the differential diagnosis between
these tumors and epithelial lesions. In the new WHO classification and
in the third series of the Armed Forces Institute of Pathology (AFIP)
"Atlas of Tumor Pathology" on urinary bladder tumors, various
mesenchymal tumors, mixed epithelial and mesenchymal tumors and
myofibroblastic proliferations are summarized. In the following we will
describe the histology, immunohistology, and cytogenetics of
nonepithelial tumors and lesions.
10
UI - 11889593
AU - Helpap B; Kloppel G
TI -
Neuroendocrine carcinomas of the prostate and urinary bladder: a
diagnostic and therapeutic challenge.
SO - Virchows Arch 2002 Mar;440(3):241-8
AD - Department of Pathology, Academic Hospital of the University of
Freiburg, Postfach 720, 78207 Singen, Germany.
pathologie@hegau-klinikum.de
This review addresses the various morphological, immunohistochemical and
cell kinetic aspects of pure and mixed neuroendocrine carcinomas of the
prostate and urinary bladder and of carcinomas with focal neuroendocrine
differentiation. It is important that neuroendocrine tumours of the
prostate and urinary bladder be clearly distinguished from their
nonneuroendocrine counterparts because of differences in treatment and
prognosis. In the case of high-grade neuroendocrine carcinomas, early
diagnosis and initiation of appropriate chemotherapy may increase
survival and potentially induce complete remission in individual cases.
11
UI - 11996795
AU - Tsukamoto M; Matsuyama H; Oba K; Yoshihiro S; Takahashi M; Naito K
TI -
Numerical aberrations of chromosome 9 in bladder cancer. A possible
prognostic marker for early tumor recurrence.
SO - Cancer Genet Cytogenet 2002 Apr 1;134(1):41-5
AD - Department of Urology, Yamaguchi University School of Medicine, Ube,
Japan.
To investigate whether nonrandom aberrations of chromosomal numbers
could predict tumor recurrence in patients with bladder cancer, archival
urine cytology specimens (Giemsa-stained) from patients previously
treated for transitional cell carcinoma of the urinary bladder were
studied retrospectively by fluorescence in situ hybridization. A total
of 48 patients (pTis, 6; pTa, 2: pT1, 32; and pT2-4, 8) were
consecutively enrolled in this study, and numerical aberrations of
chromosomes 9 and 17 were investigated. Cytology was diagnosed as
negative for malignancy in 18 patients and positive in 30 patients.
Twenty-seven of the 48 patients (56%) had one or more chromosomal
aberrations. The frequency of numerical aberrations of chromosome 17 was
correlated with increasing stage and grade, whereas loss of copies of
chromosome 9 (monosomy) was frequently observed at a lower stage and
grade. Chromosomal aberrations were detected in 9 (50%) of 18 patients
with negative or equivocal cytology (class I, II, or III) by the
Papanicolaou classification. Of eight patients with negative or
equivocal cytology who developed tumor recurrence, four (50%) showed
monosomy 9 and one (14%) showed a numerical aberration of chromosome 17.
All six patients who showed monosomy of chromosome 9 developed tumor
recurrence within 12 months, whereas four of the nine patients who did
not show monosomy of this chromosome developed recurrence within 12
months (P<0.05, Fisher test). These results suggest that monosomy of
chromosome 9 might be a prognostic marker for early tumor recurrence in
patients with negative or equivocal cytology specimens.
12
UI - 11796234
AU - de Braud F; Maffezzini M; Vitale V; Bruzzi P; Gatta G; Hendry WF;
TI -
Sternberg CN
Bladder cancer.
SO - Crit Rev Oncol Hematol 2002 Jan;41(1):89-106
AD - START Project, European School of Oncology, Viale Beatrice d'Este 37,
20122 Milan, Italy.
Bladder cancer is the second most frequent tumour of the urogenital
tract. Tobacco smoke has been shown to increase the risk of bladder
cancer two- to fivefold as well as the exposure to metabolites of
aniline dyes and other aromatic amines. Seventy-five per cent of bladder
cancers are superficial at initial presentation, limited to the mucosa,
submucosa, or lamina propria. Recurrence rates after initial treatment
are 50-80%, with progression to muscle-invading tumour in 10-25%. In
muscle-invading bladder cancers, there is a 50% risk of distant
metastases. Surgery is the mainstay of standard treatment both in the
form of transurethral endoscopic resection, mainly for superficial
disease, and in the form of open ablative surgery with urinary diversion
for muscle invasive disease. Endovesical administration of BCG has been
employed after endoscopic resection as the most effective agent for both
prophylaxis of disease recurrence and progression from superficial to
invasive disease. The accepted treatment for muscle infiltrative disease
is radical cystectomy. Response rates to combination chemotherapy
regimens of up to 70% in patients with advanced metastatic disease have
led to an investigation of its use for locally invasive disease in
combination with conventional modalities of treatment.
13
UI - 11953885
AU - Turner KJ; Crew JP; Wykoff CC; Watson PH; Poulsom R; Pastorek J;
TI -
Ratcliffe PJ; Cranston D; Harris AL
The hypoxia-inducible genes VEGF and CA9 are differentially regulated in
superficial vs invasive bladder cancer.
SO - Br J Cancer 2002 Apr 22;86(8):1276-82
AD - ICRF Molecular Oncology Laboratory and Angiogenesis Group, Institute of
Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Regulation by hypoxia may underlie the expression of vascular
endothelial growth factor in bladder cancer. We have compared the
distribution of vascular endothelial growth factor mRNA with a hypoxia
marker, carbonic anhydrase 9 (CA IX). vascular endothelial growth factor
mRNA was analysed by in situ hybridisation and CA IX by immunochemistry
in 22 cases of bladder cancer. The relationship of microvessels to the
distribution of CA IX was determined. In a separate series of 49
superficial tumours, CA IX immunostaining was compared with
clinico-pathological outcome. In superficial and invasive disease there
was overlap in the expression of vascular endothelial growth factor and
CA IX, CA IX being more widespread. Both were expressed predominantly on
the luminal surface, and surrounding areas of necrosis (invasive
tumours). Expression of both factors was greater in superficial disease.
Expression was absent within approximately 80 microm of microvessels.
Unlike vascular endothelial growth factor, CA IX did not predict outcome
in superficial disease. Differential responses to reoxygenation provide
one explanation: vascular endothelial growth factor mRNA declined
rapidly, while CA IX expression was sustained for >72 h. Expression of
vascular endothelial growth factor mRNA in bladder tumours is consistent
with hypoxic regulation and suggests differential regulation in
superficial vs invasive disease. The expression of CA IX on the luminal
surface justifies investigation of its utility as a therapeutic
target/prognostic indicator. Copyright 2002 Cancer Research UK
14
UI - 11953886
AU - Dangles V; Lazar V; Validire P; Richon S; Wertheimer M; Laville V;
TI -
Janneau JL; Barrois M; Bovin C; Poynard T; Vallancien G; Bellet D
Gene expression profiles of bladder cancers: evidence for a striking
effect of in vitro cell models on gene patterns.
SO - Br J Cancer 2002 Apr 22;86(8):1283-9
AD - Laboratoire d'Immunologie des Tumeurs, ESA 8067 CNRS, Faculte des
Sciences Pharmaceutiques et Biologiques de Paris, Universite Paris
V-Rene Descartes, 4 avenue de l'Observatoire, 75006 Paris, France.
In order to assess the effect of in vitro models on the expression of
key genes known to be implicated in the development or progression of
cancer, we quantified by real-time quantitative PCR the expression of 28
key genes in three bladder cancer tissue specimens and in their derived
cell lines, studied either as one-dimensional single cell suspensions,
two-dimensional monolayers or three-dimensional spheroids. Global
analysis of gene expression profiles showed that in vitro models had a
dramatic impact upon gene expression. Remarkably, quantitative
differences in gene expression of 2-63-fold were observed in 24 out of
28 genes among the cell models. In addition, we observed that the in
vitro model which most closely mimicked in vivo mRNA phenotype varied
with both the gene and the patient. These results provide evidence that
mRNA expression databases based on cancer cell lines, which are studied
to provide a rationale for selection of therapy on the basis of
molecular characteristics of a patient's tumour, must be carefully
interpreted. Copyright 2002 Cancer Research UK
15
UI - 11992840
AU - Yang MH; Chen KK; Yen CC; Wang WS; Chang YH; Huang WJ; Fan FS; Chiou TJ;
TI -
Liu JH; Chen PM
Unusually high incidence of upper urinary tract urothelial carcinoma in
Taiwan.
SO - Urology 2002 May;59(5):681-7
AD - Division of Medical Oncology, Department of Medicine, Taipei Veterans
General Hospital and National Yang-Ming University School of Medicine,
Taipei, Taiwan, Republic of China.
OBJECTIVES: Unusually high incidences of upper urinary tract urothelial
carcinoma (UUT-UC) have been reported from the endemic area for
"blackfoot disease" of southern Taiwan, and the arsenic-contaminated
water was considered to be the reason for this prevalence. In this
study, we determined the ratio of UC in different locations, the
difference in clinical profiles for UUT-UC and urinary-bladder
urothelial carcinoma (UB-UC), and the influence of tumor location on
survival in a medical center of northern Taiwan. METHODS: A total of 535
patients with pathologically proven UC were reviewed retrospectively in
this study, and clinical data were recorded from pathologic and chart
reviews. Statistical analyses to determine the association between tumor
location and clinical variables, and stratified survival analyses to
determine the effect of tumor location on survival were performed.
RESULTS: The incidence of UUT-UC was relatively high (the ratio of renal
pelvis/ureter/urinary bladder was 1:2.08:6.72), even though most of the
patients did not reside in the endemic "blackfoot disease" area. Young
age, female sex, higher T stage, and elevated pretreatment serum lactate
dehydrogenase and creatinine level were significantly associated with
UUT-UC after multivariate logistic regression analysis. Tumor location
influenced survival in patients with early-stage disease or favorable
prognostic factors. CONCLUSIONS: Factors other than arsenic water
contamination may contribute to the unusually high incidence of UUT-UC
in the non-"blackfoot disease" area in Taiwan. UUT-UC carried a more
aggressively clinical behavior than UB-UC; tumor location influences
patient survival markedly in patients with early-stage disease or
favorable prognostic factors.
16
UI - 11389545
AU - Veltri RW; Partin AW; Miller MC
TI -
Quantitative nuclear grade (QNG): a new image analysis-based biomarker
of clinically relevant nuclear structure alterations.
SO - J Cell Biochem Suppl 2000;Suppl 35():151-7
AD - Research & Development, UroCor, Inc., 840 Research Parkway, Oklahoma
City, OK 73104, USA. rveltri@urocor.com
This review addresses the potential clinical value of using quantitative
nuclear morphometry information derived from computer-assisted image
analysis for cancer detection and predicting outcomes such as tumor
stage, recurrence, and progression. Today's imaging technology uses
sophisticated hardware platforms coupled with powerful and user-friendly
software packages that are commercially available as complete image
analysis systems. There are many different mathematically derived
nuclear morphometric descriptors (NMD's) (i.e. texture features) that
can be calculated by these image analysis systems, but for the most
part, these NMD's quantify nuclear size, shape, DNA content (ploidy),
and chromatin organization (i.e. texture, both Markovian and
non-Markovian) parameters. We have utilized commercially available image
analysis systems and the NMD's calculated by these systems to create a
mathematical solution, termed quantitative nuclear grade (QNG), for
making clinical, diagnostic, and prognostic outcome predictions in both
prostate and bladder cancer. A separate computational model is
calculated for each outcome of interest using well-characterized and
robust training, testing, and validation patient sample sets that
adequately represent the selected population and clinical dilemma. A
specific QNG solution may be calculated either by non-parametric
statistical methods or non-linear mathematics employed by artificial
neural networks (ANNs). The QNG solution, a measure of genomic
instability, provides a unique independent variable to be used alone or
to be included in an algorithm to assess a specific clinical outcome.
This approach of customization of the nuclear morphometric descriptor
(NMD) information through the calculation of a QNG solution
mathematically adjusts for redundancy of features and reduces the
complexity of the inputs used to create decision support tools for
patient disease management. J. Cell. Biochem. Suppl. 35:151-157, 2000.
Copyright 2001 Wiley-Liss, Inc.
17
UI - 11839665
AU - Chan MW; Chan LW; Tang NL; Tong JH; Lo KW; Lee TL; Cheung HY; Wong WS;
TI -
Chan PS; Lai FM; To KF
Hypermethylation of multiple genes in tumor tissues and voided urine in
urinary bladder cancer patients.
SO - Clin Cancer Res 2002 Feb;8(2):464-70
AD - Department of Anatomical and Cellular Pathology, The Chinese University
of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong
Kong SAR, People's Republic of China.
PURPOSE: We aimed to investigate the methylation pattern in bladder
cancer and assess the diagnostic potential of such epigenetic changes in
urine. EXPERIMENTAL DESIGN: The methylation status of 7 genes (RARbeta,
DAPK, E-cadherin, p16, p15, GSTP1, and MGMT) in 98 cases of bladder
transitional cell carcinoma and 4 cases of carcinoma in situ was
analyzed by methylation-specific PCR. Twenty-two cases had paired voided
urine samples for analysis. RESULTS: In transitional cell carcinoma
tumor tissues, aberrant methylation was frequently detected in RARbeta
(87.8%), DAPK (58.2%), E-cadherin (63.3%), and p16 (26.5%), whereas
methylation of p15 (13.3%), GSTP1 (5.1%), and MGMT (5.1%) is not common.
No association between methylation status and grading or muscle
invasiveness was demonstrated. In 22 paired voided urine samples of
bladder cancer, methylation of DAPK, RARbeta, E-cadherin, and p16 could
be detected in 45.5%, 68.2%, 59.1%, and 13.6% of the cases,
respectively. The sensitivity of methylation analysis (90.9%) was higher
than that of urine cytology (45.5%) for cancer detection. Methylation of
RARbeta(50%), DAPK (75%), and E-cadherin (50%) was also detected in
carcinoma in situ. In 7 normal urothelium samples and 17 normal urine
controls, no aberrant methylation was detected except for RARbeta
methylation in 3 normal urothelium samples (42.9%) and 4 normal urine
samples (23.5%), respectively. CONCLUSIONS: Our results demonstrated a
distinct methylation pattern in bladder cancer with frequent methylation
of RARbeta, DAPK, E-cadherin, and p16. Detection of gene methylation in
routine voided urine using selected markers appeared to be more
sensitive than conventional urine cytology.
18
UI - 11839666
AU - Onita T; Ji PG; Xuan JW; Sakai H; Kanetake H; Maxwell PH; Fong GH;
TI -
Gabril MY; Moussa M; Chin JL
Hypoxia-induced, perinecrotic expression of endothelial Per-ARNT-Sim
domain protein-1/hypoxia-inducible factor-2alpha correlates with tumor
progression, vascularization, and focal macrophage infiltration in
bladder cancer.
SO - Clin Cancer Res 2002 Feb;8(2):471-80
AD - Department of Surgery, University of Western Ontario, London, Ontario,
N6A 4G5 Canada.
Endothelial Per-ARNT-Sim (PAS) domain protein-1
(EPAS-1)/hypoxia-inducible factor-2alpha (HIF-2alpha) is a member of the
basic helix-loop-helix/PAS domain protein family and is considered to be
an endothelial-specific, hypoxia-inducible transcription factor. Because
hypoxia is a fundamental element of tumor biology determining clinical
outcome, we performed an immunohistochemical study of EPAS-1 expression
in a cohort of bladder cancer cases and assessed the possible
correlation of EPAS-1 expression with tumor hypoxia and growth. In the
67 cases (37 radical cystectomy and 30 transurethral resection) studied,
overexpression of EPAS-1/HIF-2alpha protein was not found in cancer
cells or in normal tissues but was mostly found in stroma around cancer
cells, and strong positive staining was noted in perinecrotic regions.
The perinecrotic/tumorous expression of EPAS-1/HIF-2alpha was correlated
statistically with higher histological grade (P < 0.001), advanced
pathological T stage (P < 0.001), and presence of necrosis (P < 0.001).
A parallel immunohistochemical analysis of a marker gene of vascular
endothelial growth factor demonstrated its positive correlation with
tumor grade, stage, and EPAS-1/HIF-2alpha overexpression, supporting the
correlation of EPAS-1/HIF-2alpha up-regulation with tumor angiogenesis.
To further clarify the relationship between hypoxia and vascularity in
the perinecrotic/tumorous area with EPAS-1/HIF-2alpha expression, tissue
microvessel density (MVD) was assessed. No significant correlation (P =
0.442) was found between EPAS-1/HIF-2alpha expression and MVD if the 67
tumors of different stages were all included. However,
EPAS-1/HIF-2alpha-positive cases had lower MVD than
EPAS-1/HIF-2alpha-negative cases (P = 0.001) if only invasive cancer
cases were analyzed. In addition, in all EPAS-1/HIF-2alpha-positive
staining cases, EPAS-1/HIF-2alpha-positive foci had lower MVD than
EPAS-1/HIF-2alpha-negative foci (P < 0.001). Finally, using serial
sections, the location of EPAS-1/HIF 2alpha expression was identified
mainly in tumor-associated macrophage (TAM) as well as in some
fibroblast cells. Focal TAM infiltration was identified at a higher
level in EPAS-1-positive cases than EPAS-1-negative cases (P < 0.001).
This is the first clinical report suggesting that hypoxia-induced,
perinecrotic EPAS-1/HIF-2alpha expression is correlated with tumor
progression and angiogenesis at higher grade and stage through focal TAM
infiltration in invasive bladder cancer.
19
UI - 11920732
AU - Edwards J; Duncan P; Going JJ; Watters AD; Grigor KM; Bartlett JM
TI -
Identification of loci associated with putative recurrence genes in
transitional cell carcinoma of the urinary bladder.
SO - J Pathol 2002 Apr;196(4):380-5
AD - University Department of Surgery, Glasgow Royal Infirmary, Glasgow, G31
2ER, UK.
Following an earlier study linking monosomy 9 with recurrence of
transitional cell carcinomas (TCCs) of the urinary bladder, 109 primary
and recurrent TCCs (from 47 patients) were examined to explore genetic
alterations at chromosome 9 associated with recurrence. Patient DNA was
microdissected and extracted from archival tissue sections and analysed
for loss of heterozygosity (LOH) at three regions on chromosome 9 where
tumour suppressor genes (TSGs) are known to reside (INK 4A, DBC1, and
TSC1). Patients were categorized into two groups, non-recurrent TCC (NR,
n=18) and recurrent TCC (REC, n=29). It was noted that 12% of NR
tumours, compared with 54% of REC primary tumours (p=0.01), had LOH at
all informative markers spanning the TSC1 region. The risk of recurrence
was significantly higher in patients with deleted TSC1 than in those who
retained the TSC1 region (p=0.035). Levels of LOH at DBC1 or INK 4A were
not significantly different in NR tumours than in REC primary tumours
and recurrence-free survival was not affected by loss of either of these
genes. Loss of all informative markers spanning chromosome 9 was
observed in 0% of NR tumours compared with 25% of REC primary tumours
(p=0.04). The probability of recurrence was also significantly increased
in patients who had LOH at all informative markers spanning chromosome 9
(p=0.016), confirming earlier fluorescence in situ hybridization
results. This study provides further evidence that recurrence in bladder
cancer is a distinct event, with underlying molecular causes. It also
identifies the TSC1 locus as a candidate for a TSG, which drives
recurrence in a proportion of TCC patients. Loss of all informative
markers, including those residing in the TSC1 region, spanning
chromosome 9 was also linked to recurrence. Copyright 2002 John Wiley &
Sons, Ltd.
20
UI - 11890237
AU - Herr HW
TI -
Does cystoscopy correlate with the histology of recurrent papillary
tumours of the bladder?
SO - BJU Int 2001 Nov;88(7):683-5
AD - Department of Urology, Memorial Sloan-Kettering Cancer Center, New York,
NY, USA.
OBJECTIVE: To correlate the cystoscopic appearance of recurrent
papillary bladder tumours with the histology after transurethral
resection, and thus ascertain whether cystoscopy can reliably identify
low-grade, noninvasive papillary tumours suitable for outpatient
fulguration. PATIENTS AND METHODS: In all, 150 recurrent papillary
tumours of the bladder identified at outpatient flexible cystoscopy were
classified as either low-grade and noninvasive (TaG1), high-grade and
noninvasive (TaG3), or invasive (TIG3) tumours, and correlated with
urine cytology and histology of tumour stage and tumour grade after
transurethral resection. RESULTS: Cystoscopy classified 84 of the 150
papillary tumours as TaG1 and 66 as either TaG3 or T1G3. Cystoscopy
correctly predicted the histology of 78 of 84 (93%) TaG1 tumours, 71 of
72 (98%) TaG1 tumours associated with a negative urine cytology, and 92%
of TaG3 or T1G3 tumours. CONCLUSIONS: A skilled urologist can identify
noninvasive, low-grade recurrent papillary bladder tumours on follow-up
cystoscopy that do not require biopsy and that may be treated by
outpatient fulguration alone.
21
UI - 11890238
AU - Simms MS; Perkins AC; Price MR; Scholfield DP; Bishop MC
TI -
99mTechnetium-C595 radioimmunoscintigraphy: a potential staging tool for
bladder cancer.
SO - BJU Int 2001 Nov;88(7):686-91
AD - Department of Urology, City Hospital Nottingham, UK.
msimms@gertrude42.freeserve.co.uk
OBJECTIVES: To assess whether immunoscintigraphy using a conjugate of
the anti-MUC1 monoclonal antibody C595 and 99mTc could be used to target
transitional cell bladder cancer after intravenous administration to
patients. PATIENTS AND METHODS: Twenty-one patients with invasive or
metastatic transitional cell carcinoma were recruited. Patients received
1 mg of C595 labelled with 800 MBq 99mTc followed by imaging at 0.5, 6
and 24 h using a combination of planar and single-photon emission
computed tomography. Of these patients, 14 subsequently underwent
cystectomy, four underwent radiotherapy and the remaining three had
histologically confirmed metastatic disease. The results of
immunoscintigraphy were compared with surgical findings and conventional
radiology. RESULTS: There were no adverse reactions in any patient. Of
the 20 patients who were found to have tumour at the time of the study,
positive localization of antibody in tumour was apparent in 16. Of the
remaining four patients, false-positive localization of antibody in
presumed nodal tissue was detected in two. The remaining scan results
were equivocal. In three patients, histologically confirmed pelvic nodal
metastases that had not been detected on preoperative computed
tomography were identified. CONCLUSION: These early results show the
potential of 99mTc-C595 immunoscintigraphy for staging bladder cancer. A
larger study is needed to fully evaluate the technique.
22
UI - 11890239
AU - Poulakis V; Witzsch U; De Vries R; Altmannsberger HM; Manyak MJ; Becht E
TI -
A comparison of urinary nuclear matrix protein-22 and bladder tumour
antigen tests with voided urinary cytology in detecting and following
bladder cancer: the prognostic value of false-positive results.
SO - BJU Int 2001 Nov;88(7):692-701
AD - Department of Urology and Paediatric Urology, Hospital Nordwest,
Academic Hospital of Johann-Wolfgang-Goethe-University Frankfurt,
Frankfurt/Main, Germany. poulakis@em.uni-frankfurt.de
OBJECTIVES: To evaluate the diagnostic and prognostic value of the
nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat)
tests compared with voided urinary cytology (VUC) in detecting and
following bladder cancer, assessing particularly the prognostic value of
false-positive test results in patients followed up for bladder cancer.
PATIENTS AND METHODS: From 739 patients suspected of having bladder
cancer, voided urine samples for the NMP22 and BTAstat tests, and for
VUC and urine analysis, were collected before cystoscopy. All patients
underwent transurethral resection of bladder lesions or mapping. and
were followed for a mean (range) of 27.3 (3-65) months. RESULTS: In the
406 patients with bladder cancer, the overall sensitivity was 85% for
NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1-3 the
sensitivity in detecting transitional cell carcinoma was 82%, 89% and
94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for
VUC, respectively. Although the sensitivity in detecting invasive
carcinoma was >85% for all the tests. NMP22 and BTAstat were
statistically more sensitive than VUC for superficial tumours. The
optimal threshold value for NMP22, calculated using the receiver
operating characteristics curve was 8.25 U/mL. The specificity was 68%
for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC
remained >87% and was independent of benign histological findings. In
contrast, in patients with no apparent genitourinary disease on
histology, NMP22 and BTAstat had significantly higher specificity (94%
and 92%, respectively: P=0.003) than in the group with chronic cystitis
(52% for both tests). Forty patients having no bladder cancer at biopsy
had a recurrence after a mean (range) follow-up of 7.7 (3-15) months:
all had a previous history of bladder cancer. According to subsequent
recurrence, the prognostic positive and negative predictive values were
18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC.
Both false-positive VUC and NMP22 tests predicted recurrence (log-rank
test, P<0.001 and P=0.004, respectively), but the BTAstat test produced
no similar correlation (P=0.778). CONCLUSION: The NMP22 and BTAstat
tests are better than VUC for detecting superficial and low-grade
bladder cancer but they have significantly lower specificity. After
excluding diseases with the potential to interfere in these tests the
overall specificity of both tests is increased considerably.
False-positive results from NMP22 and VUC but not from BTAstat in
patients followed up for bladder cancer correlate with future
recurrences.
23
UI - 11912378
AU - Holmang S; Johansson SL
TI -
Stage Ta-T1 bladder cancer: the relationship between findings at first
followup cystoscopy and subsequent recurrence and progression.
SO - J Urol 2002 Apr;167(4):1634-7
AD - Department of Urology, Sahlgrenska University Hospital, Goteborg,
Sweden.
PURPOSE: We studied the relationship of first cystoscopy findings with
recurrence and progression rates in a large, population based series of
patients with bladder cancer. MATERIALS AND METHODS: All 463 patients
with an initial diagnosis of stage Ta-T1 bladder cancer in western
Sweden in 1987 to 1988 were followed at least 5 years. The 355 patients
who were treated with transurethral resection only until repeat
cystoscopy or longer were selected for this report. RESULTS: Negative
first cystoscopy findings were associated with significantly decreased
recurrence and progression rates for all grades, and for stage Ta and T1
tumors. However, some patients with initial high grade carcinoma (WHO 2
to 3) had stage progression despite negative first cystoscopy. On
multivariate analyses first cystoscopy findings and papillary urothelial
neoplasm of low malignant potential versus grades 1 to 3 but not stage
and the number of tumors had prognostic significance for time to
recurrence. Only first cystoscopy findings and grade had prognostic
significance for time to stage progression. CONCLUSIONS: Our data
support other groups who recommend a less intense cystoscopy followup
schedule in patients with negative cystoscopy findings 3 months after
initial transurethral bladder resection. We recommend that patients with
initial papillary urothelial neoplasm of low malignant potential and low
grade carcinoma (WHO 1) with negative first cystoscopy findings undergo
repeat cystoscopy at month 12. In our opinion followup should not be
less intense in patients with high grade carcinoma (WHO 2-3), even in
those with stage pTa disease.
24
UI - 11836583
AU - Junker K; Kania K; Fiedler W; Hartmann A; Schubert J; Werner W
TI -
Molecular genetic evaluation of fluorescence diagnosis in bladder
cancer.
SO - Int J Oncol 2002 Mar;20(3):647-53
AD - Department of Urology, Friedrich-Schiller-University, D-07743 Jena,
Germany. kerstin.junker@med.uni-jena.de
Fluorescence diagnosis of superficial bladder cancer using
5-aminolevulinic acid (ALA) is a highly sensitive technique (95%).
However, the specificity is only 60-70% due to false-positive results
after histopathological examination. We hypothesized that the biopsies
in fluorescence endoscopy could represent early preneoplastic lesions
not detectable by histopathology. In order to evaluate the specificity
of fluorescence endoscopy at the molecular genetic level we performed
comparative genomic hybridization (CGH) and investigated telomerase
activity of ALA-positive tissue samples. For CGH, DNA was isolated from
5-10 frozen sections. Tumor and normal (control) DNAs were amplified by
DOP-PCR and labeled with biotin-dUTP and digoxigenin-dUTP, respectively.
Hybridization and detection were carried out according to standard
protocols. Telomerase activity was analyzed using a non-radioactive
system (TRAP-assay). In 33 out of 118 bladder cancer cases (28%)
detected by conventional cystoscopy, additional suspicious areas were
found using ALA. CGH revealed genetic changes in 27% of samples with
non-malignant histological diagnoses. Telomerase activity was found in
59% of these samples. Tumor samples showed genetic alterations in 84%
and in 69% telomerase activity occurred. The type of genetic alterations
in the normal biopsies was identical to the tumors. Based on these
molecular data, the portion of false-positive results obtained by
fluorescence diagnosis is lower than defined by histopathology alone.
Genetic alterations and activation of telomerase activity are early
events of tumor development in bladder cancer occurring earlier than
histological features of neoplasia. The clinical importance of
fluorescence diagnosis and the possible reduction of the recurrence rate
have to be shown in ongoing clinical studies.
25
UI - 11956100
AU - Velicescu M; Weisenberger DJ; Gonzales FA; Tsai YC; Nguyen CT; Jones PA
TI -
Cell division is required for de novo methylation of CpG islands in
bladder cancer cells.
SO - Cancer Res 2002 Apr 15;62(8):2378-84
AD - Urologic Cancer Research Laboratory, Department of Biochemistry and
Molecular Biology, University of Southern California/Norris
Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA
90089-9181, USA.
Cell division is essential for tumor development and progression.
Methylation-mediated silencing caused by aberrant de novo methylation of
CpG islands located in the promoter regions of growth regulatory genes
occurs frequently in human cancers. We investigated the relationship
between cell division and de novo methylation to determine whether de
novo methylation can occur in the absence of cell division in cancer
cells. We treated T24 bladder carcinoma cells with
5-Aza-2'-deoxycytidine to induce a transient demethylation and then
compared the timing and kinetics of remethylation of the p16 gene locus
under conditions of either G(0)-G(1) growth arrest induced by serum
starvation and confluence or continuous cell proliferation in complete
medium. Variable levels of remethylation were de
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