Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007138 (transitional cell carcinoma)
 3,949 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the immunoreactivity for bcl-2 oncoprotein in 154 cases of transitional cell carcinoma of the upper urinary tract (TCC-UUT) and its relation with the immunoreactivity for p53 oncoprotein and proliferating cell nuclear antigen (PCNA) immunoreactivity. Immunohistochemically, bcl-2 oncoprotein was recognized as positive in 29.2% of the samples. The immunoreactivity for bcl-2 oncoprotein was significantly (P < 0.05) correlated only with stage, though there was a borderline correlation (P = 0.050) with PCNA immunoreactivity. Furthermore, in invasive TCC the immunoreactivity for bcl-2 oncoprotein was associated with PCNA immunoreactivity (P < 0.041). The 5-year disease-free and overall survival rates were 55.7% and 71.5%, respectively. A univariate analysis of survival revealed that stage, grade, pattern of growth, immunoreactivity for p53 oncoprotein, and PCNA immunoreactivity each had a significant effect on disease-free and overall survival rates, whereas the immunoreactivity for bcl-2 oncoprotein had no significant effect on either rate. In the final models of the multivariate analysis, stage was found to be the only prognostic factor for disease-free survival and for overall survival. Detection of immunoreactivity for bcl-2 oncoprotein appears to be of no real value in deciding the prognosis of TCC-UUT.
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PMID:Expression of bcl-2 oncoprotein in transitional cell carcinoma of the upper urinary tract. 964 44

We have used microdissection of paraffin-embedded histological sections and polymerase chain reaction (PCR)-based direct DNA sequencing for 54 transitional cell carcinoma (TCC) of the bladder, to examine critically the association between TP53 nuclear accumulation determined by immunohistochemistry and the presence of TP53 mutations, and to examine their relationship to tumour stage and grade, as well as patient survival. There was a significant association between the presence of TP53-positive nuclei (> 10%) and a higher histological stage and grade (P = 0.0115, P = 0.0151 respectively; Fisher's exact). A significant association between TP53 gene mutations and TP53 nuclear reactivity in more than 10% of tumour cell nuclei was also observed (P = 0.0003; Fisher's exact). Mutations were detected in 18/54 (33%) cases together with the wild-type sequence when analysed from bulk frozen samples, with significant clustering of mutations in exons 7 and 8. The microdissection method distinguished more clearly between heterozygous and/or homozygous alterations of the TP53 tumour-suppressor gene, and clearly showed frequent accumulation of TP53 in the absence of mutations. When microdissecting immunonegative regions from the same paraffin sections, three out of ten samples showed the identical mutations detected in the immunopositive regions. There was a significant association between TP53 immunoreactivity in more than 50% of tumour cell nuclei and decreased survival among all patients (P = 0.0325; log-rank test). The patients with TP53 mutations showed a trend for a shorter survival period; however, the association was not statistically significant at the 95% confidence level (P = 0.132; log-rank test). In conclusion, our observations show that accumulation of TP53 occurs frequently in the absence of mutations, and that such accumulation is nevertheless associated with poor survival when it occurs in a high proportion (> 50%) of tumour cell nuclei.
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PMID:Alterations of TP53 in microdissected transitional cell carcinoma of the human urinary bladder: high frequency of TP53 accumulation in the absence of detected mutations is associated with poor prognosis. 964 38

Molecular studies of bladder carcinomas have aided in determining causative genetic events and the prognosis of cancers endowed with certain abnormalities. In vitro bladder cancer characterization of key cytogenetic alterations is useful for study of molecular changes that may promote oncogenic events. In our laboratory, a novel human bladder cancer cell line, BK10, has been established in vitro and passaged for more than 20 mo. This new bladder cancer cell line (BK10) was derived from bladder tissue containing grade III-IV/IV transitional cell carcinoma. Bladder cancer tissue was obtained at the time of radical cystoprostatectomy extirpation. Cell cultures derived from this surgical sample exhibited an epithelial morphology and expressed epithelial cytokeratins. Immunostains of BK10 were negative for prostate specific antigen (PSA), fibronectin, smooth muscle actin alpha, and desmin. Karyotypic analysis revealed an aneuploid chromosomal content <4n> with many numerical and structural abnormalities previously linked to bladder oncogenesis. Translocations occurred in chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, X and Y. G-banding analysis revealed rearrangements involving chromosomes 9q and 17p, and the location of the ab11 oncogene and the p53 gene, respectively. The availability of this bladder cancer cell line will provide a useful tool for the further study of bladder carcinoma oncogenesis and gene therapy.
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PMID:Isolation and characterization of a novel human bladder cancer cell line: BK10. 971 13

In recent years, significant information has been accumulated on the molecular alterations that take place during development of transitional cell carcinoma (TCC). A number of studies aimed at defining loss of heterozygosity have shown a general chromosomal instability in TCC with loss of parts of chromosome 9 at early stages of papillomas, and of chromosomes 11, 13, 3, 4, 8, 17 and 18 during further development of the tumor. Oncogenes are activated, exemplified by mutations in the ras gene family and overexpression of the c-erbB-2 gene, in a minor fraction of tumors. Alterations of tumor suppressors (involved in control of the cell cycle, DNA quality control and activation of apoptosis) seem to be frequently involved. Among these p53 has a key role, and one p53 allele is frequently lost in TCC followed by mutation of the remaining allele.These alterations are correlated with survival, disease progression, invasion and recurrence. Also frequently lost are the cell cycle control genes p16 and p15. The predictive value of this has not yet been determined. Studies of glycosylation genes have shown downregulation of the ABO gene, followed by loss of ABO blood group structures and accumulation of the Lewis cell adhesion molecules in high grade tumors. Functional proteome analysis has furthermore identified biomarkers that are correlated with grade and stage. Molecular models for TCC development can now be built, and clinical testing of these is urgently needed.
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PMID:Molecular alterations in bladder cancer. 975 95

In order to investigate if and when the bcl-2 oncoprotein is activated in bladder tumorigenesis and its relationship with p53 overexpression and patient survival, we studied bcl-2 and p53 expression immunohistochemically in matched normal urothelium, dysplasia and cancer specimens selected by step-sectioning from 54 radically resected bladders for non-metastatic transitional cell carcinoma (TCC). In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell compartment, while in moderate and severe dysplasia its expression was detectable also in the upper regions. Excess bcl-2 immunoreactivity was found in 27 (50%) of carcinomas, and a larger proportion of high-grade TCCs showed bcl-2 expression compared with that of low-grade TCCs (P < 0.05). Overexpression of p53 protein showed a increasing trend toward the progression of bladder tumorigenesis (P < 0.01) and a significant reciprocal correlation was found between bcl-2 and p53 expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With the evolution from mild dysplasia to carcinoma in individual cases, loss of bcl-2 expression was more frequently observed in superficial (P < 0.02) or low-grade carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma. Furthermore, patients with negative immunostaining for both bcl-2 and p53 in cancer lesions had a significantly more favorable prognosis compared with those with positive immunostaining for the oncoproteins (P < 0.05), although bcl-2 by itself did not predict patient survival. We suggest that aberrant activated bcl-2, which is seen earlier than p53, appears to facilitate bladder tumorigenesis and to enhance tumor aggression in some extent.
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PMID:Reciprocal expression of bcl-2 and p53 oncoproteins in urothelial dysplasia and carcinoma of the urinary bladder. 975 96

Phenacetin abuse and smoking are established risk factors for transitional cell carcinomas of the urinary tract. In the present study, we analysed exposure and the clinical course of patients who underwent nephrectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direct DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of p53 mutations was significantly higher in tumours with grades 3 and 4 than in those with grades 1 and 2 and higher in invasive than in non-invasive tumours. Furthermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in renal pelvic carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-->T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not differ significantly in patients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C-->T:A transversions (17.5% of mutations), which are considered typical of smoking-induced carcinomas at other sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the frequency and pattern of p53 mutations are similar in transitional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Although the sample size of our study does not allow definite conclusions, these data are compatible with chronic tissue damage as a causative factor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens.
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PMID:Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53 mutations and polymorphism of carcinogen-metabolising enzymes. 976 Nov 25

A prospective study which analyzes the presence of mutations in the suppressor oncogene p53 through automated genome sequentiation in 75 specimens of transitional cell carcinoma. The presence of mutations correlated to the pathological stage and cellular grade. Also, both the different types of mutations detected and the diversity of their location indicate the heterogeneity of bladder transitional cells carcinoma. The automated genome sequentiation method allows to detect both the type of mutation and the exact location. The detection of suppressor oncogene p53 mutations allows to identify those patients who may be at higher risk of disease progression and therefore those who should undergo a more intense follow-up.
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PMID:[Gene sequence analysis of suppressor oncogene p53 in bladder carcinoma]. 980 64

Bilharzial-related bladder carcinoma (BBC) is the most common malignant neoplasm in Egypt, also occurring with a high incidence in other regions of the Middle East and East Africa. The clinical and pathological features of BBC are different than those described for the conventional transitional cell carcinoma of the bladder, including the high incidence of squamous cell carcinoma reported in BBC and the fact that over 90% of BBC cases at presentation are advanced-stage tumors (P3 and P4). This study was conducted to better define the phenotypic alterations associated with BBC affecting the p53 cell cycle control pathway, including altered patterns of expression of downstream effector proteins such as mdm2 and p21/WAF1. A well-characterized cohort of 125 patients affected with bilharzial-related bladder tumors was studied. Tumors were classified as squamous carcinomas (n = 68), transitional cell carcinomas (n = 55), or adenocarcinomas (n = 2). The products encoded by TP53, mdm2, and p21/WAF1 genes were analyzed by immunohistochemistry. Furthermore, the patterns of expression of these molecules were correlated with the Ki67 proliferative index. In addition, the microanatomical distribution of programmed cell death was assessed in a subset of tumors, using the so-called terminal deoxynucleotidyl transferase-mediated nick end labeling method. p53 nuclear overexpression was identified in 25 (20%) of 125 cases. Nuclear overexpression of mdm2 was detected in 74 (59.2%) of 125 cases. There was a statistically significant association between coexpression of both p53 and mdm2 and detection of lymph node metastases (P = 0.04). p21/WAF1 expression was detected in 87 (72%) of 121 evaluable cases. A high Ki67 proliferative index was observed in 99 (86%) of 115 evaluable cases. There was a statistically significant association between high Ki67 proliferative index and mdm2-positive phenotype (P = 0.005) and deep muscle invasion (P3b; P = 0.026) as well as lymph node metastases (P = 0.039). Apoptosis was observed in terminally differentiated tumor cells identified in the superficial layers of well-differentiated squamous carcinoma or exfoliating cells in transitional lesions. However, only rare apoptotic tumor cells were found in basal or suprabasal layers as well as in the invasive elements of the neoplasms studied. These results suggest that the frequency of p53 nuclear overexpression in BBC is lower than that reported for conventional transitional cell carcinoma. Nevertheless, tumors with p53 alterations have a greater propensity to progress. The prominent number of cases displaying an mdm2-positive phenotype suggests that this may be an early incident in BBC and should be regarded as a potential oncogenic phenomenon. This is supported by the significant correlation between high Ki67 proliferative index and mdm2 overexpression. The association of an aggressive clinical course with the coexpression of both p53 and mdm2 products might be viewed as a cooperative effect that develops in tumor progression.
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PMID:Alterations affecting the p53 control pathway in bilharzial-related bladder cancer. 981 16

Thirteen of 28 patients (46%) with grade 2-3 multifocal transitional cell carcinoma (TCC) of the bladder were found to have p53 mutations using DNA sequence analysis. These were subsequently utilized as tumor-specific biomarkers. Analysis of 17 episodes of recurrence from five of the patients revealed that all but one carried the identical mutation to the primary tumor. Thirty urine samples were collected, at initial diagnosis and during follow-up screening, from eight patients with mutations over a period of 24 months. Sequence analysis of PCR products generated from DNA extracted from the urine sediments was carried out. The p53 mutation seen in the primary tumors was detectable in 24 of 30 urine samples. The remaining six cases coincided with a negative cystoscopic examination. Interestingly, 6 of the 24 urine samples in which mutations were detectable also coincided with negative cystoscopy. The results are consistent with: (a) monoclonality of multifocal TCC; (b) the spread of TCC through a seeding mechanism; and (c) the long-term persistence of tumor cell clones (up to 97 months) within the bladder, even in the absence of obvious tumor growth.
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PMID:Molecular screening of multifocal transitional cell carcinoma of the bladder using p53 mutations as biomarkers. 981 32

To assess the value of p53 mutations in predicting the progression of superficial bladder cancer [transitional cell carcinoma (TCC)] and to define exactly when p53 mutations occur in the process of tumor progression, 80 consecutive bladder washings from 26 high-risk (indicated by quantitative karyometric analysis) superficial TCC patients were examined by single-strand conformation polymorphism. Six of 13 patients who experienced clinical progression (progression to T2 or higher) were found to have a p53 mutation in one or more of their bladder washings. In the control group (no progression to invasive disease), only 1 of 13 patients had a p53 mutation. For these high-risk superficial TCC patients, the occurrence of a p53 mutation has a positive predictive value of 86% for the progression of disease. A negative predictive value of 63% was observed. Moreover, because p53 mutations were found in samples prior to progression (mean, 8 months), they could identify patients who need changes in their treatment strategies to prevent progression to invasive disease. Despite these promising results, it is obvious that to increase not only the positive predictive value but especially the negative predictive value of this procedure to predict progression, additional prognostic markers are still needed.
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PMID:Predictive value of p53 mutations analyzed in bladder washings for progression of high-risk superficial bladder cancer. 981 67


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