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G Dalbagni

Publications and source records attributed to G Dalbagni.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cigarette smoking and chromosome 9 alterations in bladder cancer.

Epidemiological studies suggest that bladder cancer may be caused by carcinogens in tobacco and certain occupational exposures. Molecular studies have shown that chromosome 9 alterations and TP53 mutations are the most frequent events in bladder cancer. To date, the relationships between epidemiological risk factors and genetic alterations have not been fully explored in bladder cancer. The purpose of this study was to explore the association between smoking and chromosome 9 aberrations in bladder cancer cases. Seventy-three patients with bladder cancer at Memorial Sloan-Kettering Cancer Center were evaluated for smoking history, occupational history, and chromosome 9 alterations. The epidemiological data were abstracted from medical charts. Patients' tumor tissues were analyzed using RFLP and microsatellite polymorphism assays for detection of chromosome 9 alterations. Elevated odds ratios (ORs) were found for chromosome 9 alterations in smokers compared to those in nonsmokers (OR = 4.2; 95% confidence interval, 1.02-17.0) after controlling for age, sex, race, occupational history, and stage of disease. The ORs were 3.6 for those smoking < or = 20 cigarettes per day and 5.8 for those smoking > 20 cigarettes per day. No association was found between occupational history and chromosome 9 alterations. This study supplies evidence suggestive of the link between smoking and chromosome 9 alterations in the etiology of bladder cancer and indicates that potential tumor suppressor genes on chromosome 9 may be involved in smoking-related bladder carcinogenesis.

Chromosome Aberrations↗
PubMed1997

Evaluation of the telomeric repeat amplification protocol (TRAP) assay for telomerase as a diagnostic modality in recurrent bladder cancer.

There is a need for the identification of an accurate test for the detection of recurrent bladder cancer. In this study, we evaluate the telomeric repeat amplification protocol (TRAP) assay for detection of telomerase as a potential new method for bladder cancer detection and compare it to voided urine cytology. A urine sample and a bladder wash were obtained from 63 patients with a history of bladder cancer. Cytological evaluation was performed on voided urine, and the TRAP assay was performed on voided urine and bladder wash. The overall clinical sensitivity of the TRAP assay, as defined by the ability to identify correctly the patients with pathologically confirmed bladder cancer, was 35% in voided urine and 50% in bladder wash, whereas the overall clinical sensitivity of voided urine cytology was 71%. The sensitivity of voided urine cytology for the papillary and noninvasive tumors (Ta) was 50%, compared to 92% for the superficially invasive tumors (T1), 62% for the muscle-invasive tumors (T2+), and 100% for the high-grade flat carcinoma in situ (Tis). The clinical sensitivity of the TRAP assay using voided urine was 46% for Ta, 50% for T1, 18% for T2+, and 20% for Tis. The sensitivity of the TRAP assay in Ta disease was similar to that of cytology (50% for cytology versus 46% for the TRAP assay). There was a strong association between the total number of exfoliated malignant cells and the sensitivity of the assay. The sensitivity of the TRAP assay in bladder washes was 44% for Ta, 67% for T1, 46% for T2+, and 43% for Tis. The TRAP assay is reproducible, highly specific, and not dependent on the expertise of the cytopathologist. These results suggest that this assay should be further investigated as a diagnostic tool for bladder cancer.

Carcinoma, Papillary↗
PubMed1996

Microsatellite instability and deletion analysis of chromosome 10 in human prostate cancer.

Despite the clinical relevance of prostate cancer, few aspects regarding the molecular alterations involved in the process of prostate carcinogenesis are clearly understood. Cytogenetic and molecular genetic studies have identified specific abnormalities in prostate tumors, mainly on chromosomes 8, 10 and 16. On the basis of these findings, we designed a study to further characterize the altered regions on chromosome 10, using 15 microsatellite markers on a population composed of 20 paired normal and primary non-metastatic prostatic-tumor samples. Overall, 65% (13/20) of the cases analyzed showed molecular alterations, mainly rearrangements and deletions. The locus presenting the highest rate of abnormalities was D1OS221, which maps to 10q23-q24. Another region with frequent alterations was 10q21, at the DIOS109 locus. There was no statistical association between microsatellite abnormalities and Gleason grade or tumor stage in the prostate cancer cases studied. These results suggest that microsatellite alterations on the long arm of chromosome 10 are non-random events occurring in prostate cancer and that they may play a role in the process of tumorigenesis in these neoplasms.

Carcinoma↗
PubMed1996

Comparative study between cytology and dot-ELISA for early detection of bladder cancer.

Schistosomiasis remains one of the major public health problems of the tropics. Conservative estimates place the number of infected individuals at about 200 millions. In Egypt, carcinoma of the urinary bladder associated with schistosomiasis is the foremost oncologic problem, because of its high frequency and the late presentation of cases. A newly developed monoclonal antibody CK1K10 to keratinized grade 1 squamous cell carcinoma was used in a dot enzyme-linked immunosorbent assay (Dot ELISA) to test urine samples of 118 patients with bladder carcinoma, 291 patients with genitourinary pathology other than bladder carcinoma, in addition to 550 healthy controls. The overall sensitivity of the dot ELISA was 90% among 118 patients with bladder carcinoma. Twenty-seven of 33 transitional cell carcinoma cases (82%), 68 of the 71 squamous cell carcinoma cases (96%), 7 of 10 undifferentiated tumors cases (70%), and 4 of 4 adenocarcinoma were positive with this assay. The specificity was 90% in our sample population. A comparative study of diagnosis by cytology and dot ELISA was carried out in 57 patients with bladder carcinoma. Dot ELISA was found to be superior as a screening tool for high risk groups (P < .001 using chi-square test). Cytology detected 21% of transitional cell carcinoma, 68% of squamous cell carcinoma, 50% of adenocarcinoma, and 86% of undifferentiated tumors. The dot ELISA assay should be useful for screening high-risk groups because it does not require sophisticated equipment, is noninvasive, does not require highly trained staff, and can be performed in less than 30 minutes.

Adenocarcinoma↗
PubMed1996

Overexpression of p53 protein in a high-risk population of patients with superficial bladder cancer before and after bacillus Calmette-Guérin therapy: correlation to clinical outcome.

PURPOSE: We have previously demonstrated that p53 overexpression is predictive of disease progression and survival in Ta, Tis, and T1 tumors. Instillation of Bacillus Calmette-Guérin (BCG) is now accepted to be the most efficient adjuvant therapy for superficial bladder carcinoma. The aim of this study was to determine if p53 status, assessed before and after intravesical BCG therapy, can predict clinical outcome in a high-risk population of patients with superficial bladder carcinoma. MATERIALS AND METHODS: We examined 196 tissue specimens from 98 patients, obtained immediately before and after intravesical BCG therapy. The pretherapy population was composed of 22 Ta, 57 Tis, and 19 T1 tumors. After BCG, 66 specimens were TO and 32 had residual tumors. Nuclear p53 overexpression was analyzed in relation to time to disease progression and disease-specific survival. RESULTS: The median follow-up duration was 44 months. The detection of nuclear p53 overexpression before BCG therapy did not predict response to BCG therapy. Pre-BCG p53 protein overexpression, response to BCG therapy, and pre-BCG stage were all independent markers of disease progression. In patients with residual disease after BCG therapy (nonresponders), multivariate analysis confirmed that posttherapy p53 overexpression was the only independent marker of disease progression. CONCLUSION: In this high-risk population of patients with superficial bladder tumors, patients who have p53 nuclear overexpression in the tumor and stage T1 disease before BCG therapy are at high risk of disease progression. Furthermore, in the group of patients with residual disease after BCG therapy, p53 status is a better predictor of disease progression than post-BCG stage.

Administration, Intravesical↗
PubMed1995

Deletion of the p16 and p15 genes in human bladder tumors.

BACKGROUND: Two genes, p16 (also known as CDKN2, INK4A, or MTS1) and p15 (also described as INK4B or MTS2), are found in tandem at chromosome 9p21. These genes are designated as candidate tumor suppressor genes because they encode proteins that function as negative cell cycle regulators. (The encoded polypeptides inactivate specific cyclin-protein kinase complexes that are required for progression through the cell cycle.) Molecular genetic studies have revealed that deletion of the p16 and p15 genes occurs frequently in cancer cell lines and in certain malignant neoplasms. PURPOSE: We evaluated the frequency of p16 and p15 gene alterations in a well-characterized cohort of human transitional cell bladder cancers, and we explored potential associations between alterations in these genes and tumor stage and/or grade. METHODS: Tumor tissue and normal tissue from 110 patients with transitional cell carcinoma of the urinary bladder were examined. The status of the p16 and p15 genes in these tissues was determined by Southern blotting and hybridization with gene-specific probes, by coupled polymerase chain reaction and single-strand conformation polymorphism analysis (PCR-SSCP), and by sequencing DNA fragments produced during PCR. Associations between alterations in the genes and tumor stage and/or grade were evaluated using the two-tailed Fisher's exact test. RESULTS: Homozygous deletion (both alleles lost) of the p16 and the p15 genes was observed in 11 and nine bladder tumors, respectively. Eight of the 11 tumors exhibiting complete loss of the p16 gene also displayed homozygous deletion of the p15 gene. Exclusive loss of either gene was detected in only three tumors. Hemizygous deletion (one allele lost, also referred to as loss of heterozygosity [LOH] of the p16 and/or p15 genes was observed in eight tumors. Rearrangement of the two genes was indicated in three additional tumors. No point mutations were identified in either gene. The overall frequency of alteration in this cohort of bladder tumors was approximately 18% for each gene (in 20 [18.3%, 95% confidence interval (CI) = 11.1%-25.6%] of 109 informative tumors for the p16 gene and in 18 [18%, 95% CI = 10.5%-25.5%] of 100 informative tumors for the p15 gene). A statistically significant association between p16 gene alteration and bladder tumors of low stage (P < .01) and grade (P < .01) was observed; a significant association between p15 gene alteration and tumors of low stage (P < .01) was also detected. CONCLUSIONS: Alteration of the p16 and p15 genes, especially coincident homozygous deletion, appears to be a common event in bladder cancer.

Aged↗
PubMed1995

Comparative genomic analysis of tumors: detection of DNA losses and amplification.

We demonstrate the use of representational difference analysis for cloning probes that detect DNA loss and amplification in tumors. Using DNA isolated from human tumor cell lines to drive hybridization against matched normal DNA, we were able to identify six genomic regions that are homozygously deleted in cultured cancer cells. When this method was applied in the reverse way, using normal DNA to drive hybridization against tumor cell DNA, we readily isolated probes detecting amplification. Representational difference analysis was also performed on DNAs derived from tumor biopsies, and we thereby discovered a probe detecting very frequent homozygous loss in colon cancer cell lines and located on chromosome 3p.

Animals↗
PubMed1994

Chromosome 9 allelic losses and microsatellite alterations in human bladder tumors.

Chromosome 9 allelic losses have been reported as a frequent and early event occurring in bladder cancer. It has been postulated that a candidate tumor suppressor gene may reside on this chromosome, alterations of which may lead to the development of a subset of superficial bladder tumors. More recently, the involvement of two different regions harboring suppressor loci, one on each of both chromosome 9 arms, has been proposed. We undertook the present study with the objectives of better defining the deleted regions of chromosome 9 in bladder tumors, as well as evaluating the frequency of microsatellite alterations affecting certain loci on this chromosome in urothelial neoplasia. Seventy-three primary bladder tumors were analyzed using a set of highly polymorphic markers, and results were correlated with pathological parameters associated with poor clinical outcome. We observed that, overall, 77% of the tumors studied showed either loss of heterozygosity for one or more chromosome 9 markers and/or microsatellite abnormalities at chromosome 9 loci. Detailed analyses showed that two regions, one on 9p at the interferon cluster, and the other on 9q associated with the q34.1-2 bands, had the highest frequencies of allelic losses. Furthermore, Ta lesions appeared to present mainly with 9q abnormalities, while T1 tumors displayed a mixture of aberrant 9p and 9q genotypes. These observations indicate that loss of heterozygosity of 9p may be associated with the development of superficial tumors with a more aggressive biological behavior or, alternatively, they may be related to early disease progression. In addition, microsatellite alterations were documented in over 40% of amplified cases. Taken together, these data suggest that two different tumor suppressor gene loci on chromosome 9 are involved as tumorigenic events in bladder cancer and that chromosome 9 microsatellite alterations are frequent events occurring in urothelial neoplasia.

Alleles↗
PubMed1994

p53 mutations in human bladder cancer: genotypic versus phenotypic patterns.

The objective of this study was to characterize the pattern of p53 mutations in bladder cancer. The sensitivity and specificity to detect these mutations using clinical material was assessed for the following assays: immunohistochemistry, restriction-fragment-length polymorphism, single-strand-conformation polymorphism, and sequencing. Discrepancies of reported results aimed at the identification of genetic alterations in the p53 gene may be due to differences in methodology, as well as to deficient morphological evaluation of the source of tissue utilized. In order to address these critical issues, we have implemented a novel experimental design that permits analysis by molecular genetics and immunopathology techniques in any given tissue specimen, allowing morphological correlation with genotypic and phenotypic characteristics of the tissue analyzed. Forty-two patients affected with bladder tumors in whom paired normal and tumor tissues were available were used for the present study. Nuclear immunoreactivities were observed in 26 out of 42 bladder tumors analyzed. Abnormal shifts in mobility were noted in 14 of the 42 cases in distinct exons, with one tumor revealing 3 mutations. There was a strong association between p53 nuclear over-expression and 17p LOH, as well as p53 nuclear over-expression and detection of mutations by SSCP and sequencing. According to receiver-operating-curve statistical analysis, the accuracy of detecting p53 mutations by IHC was estimated to be 90.3%. It is our conclusion that, when properly used, this is a highly sensitive and specific method with simple application using clinical material.

Antibodies, Monoclonal↗
PubMed1994

Bladder cancer: advances in biology and treatment.

Integrating systemic chemotherapy in the treatment of patients with invasive bladder cancer is essential to improve survival because the majority of deaths are from systemic relapse. However, as experience with invasive tumors evolves, it is clear that treatment recommendations need to be tailored to an individual patient based on metastatic risk and, ideally, sensitivity to treatment. For those with tumors that do not extend through the bladder wall, standard therapy remains radical surgery. Nevertheless, encouraging results are being reported with increasing frequency using strategies designed to preserve bladder function through a variety of means. Crucial to the recommendation of a specific approach for an individual is improving our ability to define prognosis prior to initiating treatment. Patients with a high risk of systemic recurrence generally require chemotherapy, although the optimal route of integration, pre vs. post-operatively, remains controversial. In those patients who require it, chemotherapy can be administered more safely with the concomitant administration of hematopoietic growth factors. These factors alone, however, are unlikely to improve overall survival. Crucial to the latter effort will be the identification of more active agents, improving our understanding of intrinsic and acquired resistance to chemotherapy, and better delivery of the chemotherapeutic agents currently available. Of equal importance, is the enrollment of patients in clinical trials. These can include large scale randomized comparisons with using a survival end-point, as well as new therapies in high risk populations. The latter would include patients with advanced T3b, T4 and N+ disease, with a high risk of metastatic failure, and low complete response proportions to presently available regimens.

Antineoplastic Agents↗
PubMed1994

Association of P53 nuclear overexpression and tumor progression in carcinoma in situ of the bladder.

We investigated the prevalence and clinical relevance of p53 nuclear overexpression, as detected by antibody PAb1801 and immunohistochemistry, in 33 patients with carcinoma in situ of the bladder. Median followup was 124 months. Disease progressed in 16 patients (48%) during followup. The association between p53 nuclear overexpression and tumor progression was assessed by multivariate analysis, controlling for possible confounding variables, such as patient age and sex, presence of associated stage Ta bladder tumor and adjuvant bacillus Calmette-Guerin therapy. Patients were stratified into 2 groups according to the per cent of tumor cells displaying p53 nuclear overexpression: group 1-18 with less than 20% tumor cells positive and group 2-15 with 20% or more tumor cells positive. Disease progressed in 3 patients (16.7%) in group 1 and in 13 (86.7%) in group 2 (p < 0.0001). Detection of p53 nuclear overexpression in 20% or more tumor cells was the only independent marker of tumor progression in univariate and multivariate analyses (p = 0.004, adjusted relative risk 8.6, 95% confidence interval 2 to 40). Death specifically from bladder cancer was also associated with this altered pattern of p53 expression (p = 0.01, Fisher's exact test). We conclude that p53 nuclear overexpression is an early event in bladder cancer, occurring in 48% of cases of carcinoma in situ of the bladder. Our results also suggest that p53 nuclear overexpression offers significant clinical information and may be a useful tool in the selection of therapy for patients with carcinoma in situ of the bladder.

Aged↗
PubMed1994

Clinical follow-up in 24 nonfamilial renal tumors cytogenetically characterized in tissue culture.

OBJECTIVE: This study investigates the relationship between clonal chromosomal abnormalities detected in nonfamilial renal cell carcinoma and the clinical outcome, specifically, whether or not patients whose tumors had karyotypic changes have a different prognosis than those whose tumors did not. METHOD: Fresh tumor tissue obtained from 32 cases was grown in tissue culture. Twenty four grew successfully and were harvested and multiple cells of each karyotyped. Clinical follow-up was obtained for at least five years or until the time of death. RESULTS: Fourteen of 24 cases demonstrated karyotypic abnormalities including loss of Y chromosome (64%), trisomy 7 (50%), trisomy 12 (14%), trisomy 9, 10, 14, 15, 16, and 17, monosomy 9 and 20, and long-arm deletion of chromosome 16 (1 case each). Tumors were well-differentiated in 16 cases, moderately differentiated in 5 cases, and poorly differentiated in 1 case; 13 cases were pathologic Stage I, 5 Stage II, and 6 Stage III. Thirty-three percent of the patients demonstrated clinical progression. CONCLUSIONS: No significant difference in prognosis could be found between patients with and without karyotypic abnormalities. The only clinical or pathologic difference which could be established was sex distribution. Significantly greater numbers of males had karyotypic abnormalities than females, but this could be explained by the high number of Y chromosome deletions that were detected. The lack of correlation between karyotypic abnormalities and clinical outcome may reflect a confounding factor in genetic evolution such that clinically determining chromosomal changes present early in a tumor's growth in vivo may no longer be present when the tumor is diagnosed, treated, or after it is grown in culture. This may make demonstration of such clinically significant chromosomal changes very difficult.

Adult↗
PubMed1993

Genetic alterations in bladder cancer.

To see whether genetic alterations follow a sequence of events leading to bladder cancer progression, 60 paired bladder tumours and normal tissues were analysed with polymorphic DNA markers, correlating loss of heterozygosity (LOH) at candidate tumour suppressor gene sites with pathological indices of poor clinical outcome. Distinct genotypic patterns were associated with early and late stages of bladder cancer. 9q deletions were observed in all superficial papillary tumours (Ta) and almost all tumours invading the lamina propria (T1), suggesting that this event associates with the development of superficial bladder tumours. However, 3p, 5q, and 17p deletions were absent in the Ta tumours but were identified in invasive bladder cancers. Two genetic pathways characterise the evolution of superficial bladder tumours. 9qLOH was detected in most Ta tumours, but in only 43% of muscle invasive neoplasms. Our hypothesis is that certain chromosomal abnormalities have a defined role in bladder tumour development, whereas others correlate with pathological indices of poor clinical outcome.

Alleles↗
PubMed1993

Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression.

BACKGROUND: Approximately one third of the patients with superficially infiltrative transitional cell (T1-TNM pathological staging system) bladder carcinoma who are treated with transurethral resection alone have disease progression. Despite precise pathologic staging and grading, clinical outcome in these patients is not predictable. Recent reports reveal that mutations of the p53 tumor suppressor gene (also known as TP53) occur commonly in bladder cancers. PURPOSE: The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein product(s) of the mutated p53 tumor suppressor gene are associated with tumor progression in patients with T1 bladder cancer. METHODS: We examined deparaffinized tumor tissue specimens from transurethral resection in 43 patients with T1 bladder cancer who had not received adjuvant therapy. Nuclear overexpression of p53 protein was detected by immunohistochemical analysis using the mouse monoclonal antibody PAb1801, which stains both wild-type and mutant p53 proteins. The data were then correlated with the following conventional prognostic variables: age, sex, histologic presence of associated carcinoma in situ, and vascular invasion of tumor. Disease progression rates per 100 person-years were calculated. RESULTS: Median follow-up was 119 months. None of the urothelial and stromal cells from normal bladder specimens showed nuclear overexpression of p53 protein, but patients with T1 bladder tumors could be stratified into two groups with different patterns of staining for p53 protein. Eighteen patients (42%) had no more than 20% tumor cells with positive nuclear staining (group A), while the remaining 25 patients (58%) had 20% or more tumor cells with nuclear immunoreactivity (group B). Patients in group B had a significantly lower progression-free interval (P < .001). Disease progression rates were 20.5% per year for group B and 2.5% for group A. CONCLUSION: These results suggest that T1 bladder cancers exhibiting nuclear overexpression of p53 protein have a higher probability of disease progression. This study also suggests that p53 overexpression is an important prognostic factor in these patients and may be useful in selecting appropriate therapy. IMPLICATIONS: Large prospective studies are needed to confirm these results and to evaluate nuclear overexpression of p53 protein as a prognostic marker in bladder cancer.

Adult↗
PubMed1993

Molecular genetic alterations of chromosome 17 and p53 nuclear overexpression in human bladder cancer.

We set out to define the alterations of chromosome 17 in human bladder tumors and to correlate p53 nuclear over-expression with 17p deletions in those neoplasms. We studied 60 bladder tumors by restriction fragment-length polymorphism analysis directed at five different loci on chromosome 17. The same tumors were studied with a panel of mouse monoclonal antibodies (PAb1801, PAb240, and PAb1620) to mutant and wild-type p53 proteins using immunohistochemistry. Deletion of 17p correlated with grade (p = 0.039), stage (p = 0.004), and the presence of vascular invasion (p = 0.056). None of the pathologic parameters correlated with 17q deletions. p53 nuclear overexpression correlated with grade (p = 0.027), stage (p = 0.008), vascular invasion (p = 0.021), and the presence of nodal metastases (p = 0.007). In superficial (Ta) lesions, 17p was not deleted, whereas 55% of T1 and T2-T4 tumors showed a loss of heterozygosity. Mutations of p53 as detected by immunohistochemistry were seen in superficial as well as invasive tumors, whereas loss of heterozygosity was seen only in invasive tumors. A strong correlation was found between the presence of mutation and the loss of heterozygosity of the remaining allele (p = 0.0003). Additional follow-up and further studies are required to better define the role of p53 nuclear overexpression and 17p deletions as markers of tumor progression in human bladder cancer.

Alleles↗
PubMed1992

Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer.

BACKGROUND: It has been reported that 50%-70% of patients with bladder cancer experience recurrence after initial successful treatment and about 10%-20% of these patients die of the disease. Despite precise pathologic staging and grading, we are unable to predict clinical outcome in all patients. The retinoblastoma-susceptibility (RB) gene, a prototype of tumor suppressor genes, has recently been associated with development and/or progression of bladder cancer, as well as sarcoma and small-cell lung cancer. In transitional cell carcinomas of the bladder, we have observed altered expression of the Rb gene product--a nuclear phosphoprotein thought to function as a cell cycle regulator. PURPOSE: The aim of this study was to investigate the hypothesis that altered patterns of Rb expression correlate with prognosis in bladder cancer. METHODS: Expression of the RB gene was evaluated in specimens from 48 primary bladder tumors obtained by cystectomy or transurethral resection. Rb protein expression was correlated with disease outcome in these patients. Rb expression was examined by immunohistochemistry, using the mouse monoclonal antibody Rb-PMG3-245 on frozen tissue sections. Computerized image analysis was used to quantify the level of Rb protein in individual tumor cells. RESULTS: The overall 5-year disease-free survival was 66%, with a median follow-up of 42 months. Normal levels of Rb protein expression were found in 34 patients (Rb-positive group). A spectrum of altered patterns of expression from undetectable levels to heterogeneous expression, however, was observed in 14 patients (altered Rb group). Of the 38 patients with muscle-invasive tumors, 13 were categorized as having altered expression of Rb protein. Only one of 10 patients with superficial carcinomas had altered expression of Rb protein. The 5-year survival was significantly decreased in patients with altered Rb protein compared with the survival in patients with positive Rb expression (P less than .001). CONCLUSIONS: The results suggest that tumors exhibiting decreased expression of the RB gene-coded product (Rb protein) had a more aggressive biological behavior than those that expressed the Rb protein in the majority of their tumor cells. IMPLICATIONS: This study demonstrates that altered patterns of Rb protein expression may be an important prognostic variable in patients presenting with invasive bladder cancer.

Adult↗