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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple transcriptional events take place when normal urothelium is transformed into tumor tissue. These can now be monitored simultaneously by the use of oligonucleotide arrays, and expression patterns of superficial and invasive tumors can be established. Single-cell suspensions were prepared from bladder biopsies (36 normal, 29 tumor). Pools of cells were made from normal urothelium and from pTa grade I and II and pT2 grade III and IV bladder tumors. From these suspensions, and from 10 single-tumor biopsies, labeled cRNA was hybridized to oligonucleotide arrays carrying probes for 6500 genes. The obtained expression data were sorted according to a weighting scheme and were subjected to hierarchical cluster analysis of tissues and genes. Northern blotting was used to verify the array data, and immunohistology was used to correlate between RNA and protein levels. Hierarchical clustering of samples correctly identified the stage using both 4076 genes and a subset of 400 genes covarying with the stages and grades of tumors. Hierarchical clustering of gene expression levels identified several stage-characteristic, functionally related clusters, encoding proteins that were related to cell proliferation, oncogenes and growth factors, cell adhesion, immunology, transcription, proteinases, and ribosomes. Northern blotting correlated well with array data. Immunohistology showed a good concordance between transcript level and protein staining. The study indicates that gene expression patterns may be identified in bladder cancer by combining oligonucleotide arrays and cluster analysis. These patterns give new biological insight and may form a basis for the construction of molecular classifiers and for developing new therapy for bladder cancer.
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PMID:Identification of gene expression patterns in superficial and invasive human bladder cancer. 1128 20

Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.
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PMID:High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer. 1138 83

We evaluated the genetic changes in bladder cancer biopsy by fluorescence in situ hybridization (FISH) and related them to stage and grade of the tumor, ploidy (FCM) and clinical outcome, to determine a simple method to identify tumors with a poorer prognosis. Using FISH the numerical aberrations of chromosomes 1, 7, 9, 17 in tumor's imprints of 70 patients with transitional cell cancer (TCC) were determined. First of all, the data demonstrated that the sensitivity of FISH in detecting quantitative DNA aberrations exceeds FCM's sensitivity. The frequency of chromosome 1 and 9 aberrations did not show significant differences in diploid and aneuploid tumors in different stage and grade. On the contrary, the chromosome 7 and 17 aneusomy showed greater differences between pT1 and pT2-3 tumors (p<0.032 and p<0.0006, respectively) than between stage pTa and pT1. In our investigation, an increasing number of aberrations was observed in all chromosomes examined in tumors of patients who afterwards underwent cystectomy and/or had recurrent tumors. These results suggest that chromosome 7 and 17 aneusomy could be predictive of adverse outcome in a subgroup of patients with superficial tumors at presentation.
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PMID:DNA aberrations in urinary bladder cancer detected by flow cytometry and FISH: prognostic implications. 1141 67

The aim of this study was to evaluate the UroVysion (Vysis, Downers Grove, IL) fluorescence in situ hybridization (FISH) test for improved detection of bladder cancer in urinary specimens. Three groups of specimens were examined, including voided urine specimens (1) collected before resection of bladder cancer, (2) from cystoscopically negative bladders of patients with previous bladder cancer, and (3) from patients with benign prostatic hyperplasia (controls). FISH positivity was defined as more than 2 urothelial cells with an abnormal signal copy number of at least 1 of the 4 probes. FISH was positive in 1 of 27 control specimens and in 33 (73%) of 45 pTa, 12 (100%) of 12 pT1, and 13 (100%) of 13 pT2-4 tumors. The results were similar in a series of 68 bladder washings. In addition, FISH of voided urine specimens was positive in 5 of 10 patients with negative follow-up cystoscopy results. Subsequent recurrence was found in 4 of these patients but in none of 5 patients with FISH-negative results. Multiprobe FISH markedly improves the sensitivity and specificity of cytology for the detection of bladder cancer in urine specimens.
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PMID:Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings. 1144 56

In bladder cancer the observed microsatellite instability indicates that mismatch repair deficiency could be a frequently involved factor in bladder cancer progression. To investigate this hypothesis we analysed extracts of seven bladder cancer cell lines and, as a novel approach, five clinical cancer samples for mismatch repair activity. We found that one cell line (T24) and three of the clinical samples had a reduced repair capacity, measured to approximately 20% or less. The T24 cell extract was unable to repair a G-G mismatch and showed reduced repair of a 2-base loop, consistent with diminished function of the MSH2-MSH6 heterodimer. The functional assay was combined with measurement for mutation frequency, microsatellite analysis, sequencing, MTT assay, immunohistochemical analysis and RT-PCR analysis of the mismatch repair genes MSH2, MSH3, MSH6, PMS1, PMS2 and MLH1. A >7-fold relative increase in mutation frequency was observed for T24 compared to a bladder cancer cell line with a fully functional mismatch repair system. Neither microsatellite instability, loss of repair nor mismatch repair gene mutations were detected. However, RT-PCR analysis of mRNA levels did detect changes in the ratio of expression of the Mut S and Mut L homologues. The T24 cell line had the lowest MSH6 expression level of the cell lines tested. Identical RT-PCR analysis of seventeen clinical samples (normal urothelium, 7; pTa low stage, 5; and pT1-4 high stage, 5) indicated a significant change in the expression ratio between MSH3/MSH6 (P< 0.004), MSH2/MSH3 (P< 0.012) and PMS2/MLH1 P< 0.005, in high stage bladder tumours compared to normal urothelium and low stage tumours. Collectively, the data suggest that imbalanced expression of mismatch repair genes could lead to partial loss of mismatch repair activity that is associated with invasive bladder cancer.
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PMID:Functional analysis of the mismatch repair system in bladder cancer. 1150 98

We prospectively evaluated the performance of urinary NMP22 test in the detection of transitional carcinoma (TCC) of the bladder. Urine samples were obtained from 39 patients with known bladder cancer, 37 patients with primary hematuria. 18 with benign urological conditions and 20 healthy subjects. Overall sensitivity and specificity of NMP22 with reference value of 10 U/ml was 72 and 73%, respectively. Sensitivity for pT1 and pT2 tumors was 83%, whereas that for pTa tumors was 55%. When the test was determined before and after transurethral resection (TUR) of bladder tumor, it was shown that the TUR effected the NMP22 level. Urinary NMP22 was highly sensitive for high-risk bladder cancer. However, the sensitivity of the test is somewhat lower in low grade and stage tumors. Additionally, the effect of previous resection limits its value in the follow up of patients with superficial tumors. The larger series with longer follow up may lead us to determine the time to neglect the effect of TUR on NMP22 and the test kit should be upgraded by the manufacturer to exclude the false positive results due to inflammatory conditions.
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PMID:Evaluation of nuclear matrix protein 22 (NMP22) as a tumor marker in the detection of bladder cancer. 1158 54

Transitional cell carcinoma (TCC) is the most common bladder tumor. Urine cytology can identify most high-grade tumors but sensitivity is lower if one includes lesions of all grades. Microsatellite marker alterations have been found in many tumor types including bladder cancer and have been used to detect cancer cells in body fluids including urine. The aim of our study is to further evaluate feasibility and sensitivity of microsatellite analysis to detect bladder cancer cells in urine. We studied 55 individuals: 21 with symptoms suggestive of bladder cancer, 23 patients with previous history of TCC and 11 healthy subjects. Genomic DNA was extracted from blood lymphocytes, urine sediment, bladder washings and tumor or normal bladder mucosa. Twenty highly informative microsatellite markers were analyzed for loss of heterozigosity (LOH) and microsatellite instability (MIN) by polymerase chain reaction. Microsatellite analysis of urine identified 33 of 34 (97%) patients with either primary or tumor recurrence, whereas urine cytology identified 27 of 34 (79%) patients (p = 0.0001). Detection of microsatellite abnormalities improved the sensitivity of detecting low-grade and/or stage bladder tumor: from 75-95% for grades G1-G2 and from 75-100% for pTis-pTa tumors. Bladder washings from 25 patients were also analyzed, and in all cases results were identical to those obtained from voided urine. None of the 16 patients without evidence of TCC showed LOH and/or MIN in urine samples or bladder washings. Interestingly, in a patient with persistent bladder mucosa abnormalities, microsatellite alterations were demonstrated 8 months before the histopathologic diagnosis of tumor recurrence. These results further indicate that microsatellite marker analysis is more sensitive than conventional urine cytology in detecting bladder cancer cells in urine and represents a potential clinical tool for monitoring patients with low-grade/stage TCC.
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PMID:Sensitive detection of transitional cell carcinoma of the bladder by microsatellite analysis of cells exfoliated in urine. 1166 18

Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.
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PMID:Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. 1180 96

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.
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PMID:Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer. 1197 Nov 82

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.
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PMID:Numerical aberrations of chromosome 9 in bladder cancer. A possible prognostic marker for early tumor recurrence. 1199 95


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