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)

Recent investigations have demonstrated p53 and Rb alterations in a subset of transitional cell carcinoma (TCC). Further genetic changes during tumor progression include overexpression of the c-myc gene in a significant number of mainly invasive bladder tumors. To study the possible interactions between these genes in TCC, urothelial cancer cell lines were chosen as an in vitro model. Expression and mutation of p53 was studied in 15 bladder cancer cell lines by immunocytochemistry, Western blot, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing of double stranded PCR products of exons 4, 5, 7 and 8 of genomic DNA. C-myc expression and gene structure were studied using Northern and Southern blot techniques Rb protein expression was analyzed by Western blot. Twelve of 15 cell lines showed either p53 mutations or abnormal protein expression. Consistent with previous studies, five cell lines did not express Rb protein. None of the cell lines studied retained both tumor suppressor genes in a functional form. The c-myc gene appeared to be intact in all cell lines and copy numbers were close to normal. Northern analysis demonstrated that all cell lines expressed c-myc mRNA but evidence for altered regulation was found in at least two cell lines. Our data suggest that amplification or translocation are not the underlying mechanism for c-myc overexpression in urothelial tumors. No correlation between loss of Rb protein and c-myc expression was observed. The results presented here for the cell lines match well those obtained in vivo. Thus, these cell lines may provide a suitable model for further analysis of molecular alterations in urothelial cancer.
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PMID:Inactivation of tumor suppressor genes and deregulation of the c-myc gene in urothelial cancer cell lines. 883 85

The objective of this study was to characterize the alterations of 9p21 and TP53 in Korean transitional bladder cancer and to assess the relationship between the histopathologic parameter and the alteration of these genes. Allele loss in 29 surgically resected transitional cell carcinoma was examined by using the multiplex PCR with 7 and 1 microsatellite markers for 9p21 and TP53, respectively. Twenty-one (72%) demonstrated allele loss at 9p21 and/or TP53. Deletion at the 9p21 region was detected in 17(61%) of 28 informative cases at one or more loci, and LOH at TP53 was found in 12(55%) of 22 informative cases. Of 7 microsatellite markers for 9p21, allele loss occurred the most frequently at locus D9S162(69%) and D9S104(69%). Additionally, hemizygous deletion was slightly more common than homozygous deletion. Deletion at 9p21 and TP53 was not related with increased grade. These results suggest that the alteration of 9p21 may be an early event in the development of Korean bladder cancer, while p53 gene may be involved in early event of some bladder cancers as well as in their late events.
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PMID:Deletions of 9p21 and TP53 in bladder cancer. 884 5

Alterations in the p53 gene are a predominant component in the development of transitional cell carcinoma (TCC), but the particular pathways distal to p53 alterations which contribute to urothelial transformation are not defined. Here, the p21WAF1/CIP1 gene, a p53 inducible and p53 independent gene product, was studied in TCC. p21WAF1/CIP1 expression was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from five cell lines and 28 tumor specimens (14 superficial, 14 muscle invasive). This was expressed as a ratio of the gene product to L7, a ribosomal housekeeping gene. In addition, exons 4 through 8 of the p53 gene as well as exon 2 of the p21WAF1/CIP1 gene were assayed for mutations by polymerase chain reaction/single stranded conformation polymorphism analysis (PCR/SSCP). Candidate mutations were verified by sequencing. p21WAF1/CIP1/L7 expression was significantly decreased in invasive lesions compared to superficial lesions (P<0.002). p53 mutations were detected by PCR/SSCP in seven tumors [25%] (one superficial, six invasive) and p21WAF1/CIP1/L7 expression was significantly decreased in all tumors that had p53 mutations (P<0.007). PCR/SSCP analysis of exon 2 in p21WAF1/CIP1 detected band shifts in four/28 tumor specimens (two superficial, two invasive), which sequencing and comparison to autologous normal matched DNA revealed as novel mutations.
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PMID:Novel p21WAF1/CIP1 mutations in superficial and invasive transitional cell carcinomas. 893 28

The p53 gene, which is located on human chromosome 17, encodes for a nuclear phosphoprotein and is thought to regulate cell growth and proliferation. Although the immunoreactivity for p53 oncoprotein in transitional cell carcinoma (TCC) of the urinary bladder has been shown to correlate with clinicopathologic findings and prognoses, there have been no such reports on TCC of the upper urinary tract (TCC-UUT). The present study investigated the prognostic value of p53 oncoprotein in TCC-UUT. Formalin-fixed, paraffin-embedded tumor tissues from 149 TCC-UUT patients were analyzed using immunohistochemical staining. Immunohistochemically, p53 oncoprotein was recognized as positive in 26.8% of the samples. The immunoreactivity for p53 oncoprotein was significantly (P < .05) correlated with both stage, grade, and pattern of growth. The 5-year disease-free and overall survival rates were 58.4% and 69.7%, respectively. A univariate analysis of survival showed that stage, grade, pattern of growth, and the immunoreactivity for p53 oncoprotein have a significant effect on disease-free and overall survival rates. In the final models of multivariate analysis, only stage for disease-free survival, and stage and the immunoreactivity for p53 oncoprotein for overall survival were found to be progressive or prognostic factors. Detection of immunoreactivity for p53 oncoprotein appears to be of real value in deciding the prognosis of TCC-UUT.
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PMID:Immunohistochemical evaluation of p53 oncoprotein in transitional cell carcinoma of the upper urinary tract. 895 8

Management of Transitional Cell Carcinoma (TCC) of the bladder depends on clinicopathological parameters at initial presentation. These criteria are insufficient predictors because of tumor heteterogeneity. Progress in tumor biology suggest that molecular markers may be used to dismember bladder cancer according to their biological behavior. Evidences have accumulated that cancer result from accumulation of molecular defect specially on tumor suppressor genes. In this respect we studied by mean of immunohistochemistry the prognostic value of p53 nuclear overexpression using monoclonal antibody P1801. The study was performed on 114 TTC and 13 normal bladders. Nuclear straining was quantified using an eye piece reticule at magnification 400x. Scoring was determined counting 500 nuclei in 3 to 5 arbitrary fields. Results between stage, grade and percentage of stained nuclei are as follow: TA 0,92-T1 0,144-T2 0,354-T4 0,622-G1 0,105-G2 0,212-G3 0,406. Comparison of mean nuclear straining between group with and without progression indicates a threshold of 16% for p53 nuclear overexpression. Using this limit there is a significant progression free survival rate for the all group (p < 0,0001) and for the group of superficial tumors (p = 0,0007). Multivariate analysis using stepvise logistic regression indicate a p53 prognostic value independent from stage and grade (OR 23,4). This result indicates that p53 overexpression which can be determined on routine preparation has a strong prognostic value and a certain clinical utility.
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PMID:[Evaluations of protein p53 overexpression in cancer of the bladder: prognostic value]. 897 42

Overexpression of p53, as determined by immunohistochemical staining with the murine monoclonal antibody DO7, was determined in specimens of 46 primary superficial transitional cell bladder tumours (14 TaG2, 10 T1G2, 22 T1G3). A colon cancer specimen served as a positive control and normal mesenchymal cells in the specimens served as an internal negative control. An exceptionally high proportion 36/46 (78%) of the specimens were found to stain positively for p53 in over 20% of the cell nuclei. After a median follow-up of 7 years, ten patients developed progressive disease. Of these ten patients nine demonstrated p53 positivity, resulting in a sensitivity of 90%. However, 27 of the overall 36 patients (75%) with p53-positive tumours did not progress to a higher stage or metastatic disease. These findings suggest that p53 overexpression is not of predictive prognostic value in superficial transitional cell carcinoma. With 7 of 14 specimens (50%) of Ta tumours overexpressing p53, the results were suggestive of p53 mutation being an early event in carcinogenesis. When the threshold was set at 50% of the cell nuclei overexpressing p53, 16/46 (35%) classified as p53 positive. Of the 16 tumours staining positively for p53, 7 (46%) progressed and 9 (56%) did not. None of the Ta and 16 (50%) of the T1 tumours classified as positive. This more stringent definition of positivity still does not identify p53 positivity as a single prognostic factor. With 50% of T1 tumours classifying as positive, we still find that p53 mutation may be an early event in carcinogenesis of bladder cancer.
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PMID:Immunohistochemical determination of p53 overexpression. An easy and readily available method to identify progression in superficial bladder cancer? 907 54

This report documents an uncommon case of osteoclastoma-like giant cell tumor of the renal pelvis associated with papillary transitional cell carcinoma, which resulted in the patient's death. A low-grade transitional papillary carcinoma associated with a prominent osteoclastoma-like giant cell tumor was found in the pelvicalyceal system of the right kidney in a 69-year-old man. The spindle component of the tumor stained for epithelial membrane antigen, indicating an epithelial origin. Positive staining with antibody against p53 protein was observed in both tumoral components. Our results suggest that this osteoclastoma-like giant cell tumor was truly neoplastic and that the two components could have arisen from an initial monoclonal neoplastic proliferation.
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PMID:Osteoclastoma-like giant cell tumor of the renal pelvis associated with papillary transitional cell carcinoma. 912 46

We investigated the expression of androgen receptor (AR) protein in transitional cell carcinoma of human urinary bladder in paraffin-embedded sections of tumours obtained from nine patients with urinary bladder cancer treated by radical cystectomy. In addition, immunoblotting of AR was also performed on selected samples. Nuclear immunoreactivity of AR was found in seven of the nine urinary bladder cancers studied. AR showed variable staining intensity within a tumour. In the immunoblots, a 110 kDa AR signal was seen with anti-AR antibody, and faint bands of 90 and 60 kDa were also observed. Immunohistochemistry of p53 and c-erbB-2 was also carried out and compared with the distribution of AR. The high frequency of AR expression suggests a role for androgens in transitional cell carcinoma of human urinary bladder.
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PMID:Immunodetection of androgen receptor in human urinary bladder cancer. 920 60

We analyzed p53 mutations in 17 N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder transitional cell carcinomas (TCCs) with or without areas of squamous cell carcinoma (SCC) of Long-Evans Cinnamon (LEC) and F344 rats, and in 7 N-methyl-N-nitrosourea-induced colon adenocarcinomas of LEC rats by polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing. Of these bladder tumors, one TCC with moderately differentiated SCC had a T to G transversion mutation at codon 141, leading to a Val to Gly amino acid change. No p53 mutation was found in colon adenocarcinomas. Thus a p53 gene mutation seems infrequent in these rat bladder and colon carcinogenesis models even in the late stage.
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PMID:p53 gene mutation in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder tumors and N-methyl-N-nitrosourea-induced colon tumors of rats. 923 35

In order to find the significance of gene changes in the development of transitional cell carcinoma of bladder, immunohistochemical and PCR-RFLP methods were used to study the expression of P21, P185, p53 proteins and mutations in ras and p53 genes. The results showed that the P21, P185 and p53 positive rates were 59.3%, 55.3% and 29.3% respectively. Positive rates for P21 and P185 decreased with the progression of the pathological grade (P < 0.05). p53 positive rates decreased with the progression of pathological grade (P < 0.01). Positive expression of P21, P53 were significantly correlated with prognosis. Expression of more than two kinds of oncogene proteins were present in 73 cases of bladder transitional cell carcinoma. The rate of point mutation in codon 12 of Ha-ras gene of bladder transitional cell carcinoma was 32%. The p53 gene mutation rate of bladder transitional cell carcinoma was 18%, all mutations occurred at codon 248. The point mutation in codon 12 of Ha-ras gene increased with the progression of pathological grade (P < 0.05). The ras and p53 gene mutations were significantly correlated with prognosis (P < 0.05). The mortality of patients with ras and p53 gene mutation were higher than patients without mutations. 4 cases of bladder transitional cell carcinoma contained both ras and p53 gene mutations.
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PMID:[Detection and clinical pathological significance of the expression of P21, P185, p53 proteins and mutation of ras, p53 genes in transitional cell carcinoma of the bladder]. 927 51


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