Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulation of p53 and C-Myc overexpression are frequently found in advanced urothelial carcinomas. The prevalence and predictive value of both molecular alterations was investigated in 61 patients with superficial urothelial tumors. Distinct patterns of p53 accumulation and C-Myc overexpression were observed in superficial urothelial carcinoma of different stages. For instance, 67% of carcinomata in situ displayed accumulation of p53, but only 44% showed C-Myc overexpression, whereas in pT1 tumors the corresponding percentages were 25 and 75%. Similarly, while p53 accumulation was significantly (p = 0.02) associated with tumor grade, C-Myc overexpression did not correlate with grade. In multivariate analysis, p53 accumulation was found to be an independent predictor of tumor progression (p = 0.0096), whereas C-Myc overexpression did not correlate with the course of disease. Alterations in both markers together predicted neither tumor recurrence nor tumor progression better than p53 accumulation on its own. Sufficient expression of C-Myc may be a general requirement for proliferative competence in urothelial tumors, barring its use as a predictive marker. The predictive value of p53 accumulation for tumor progression was further underlined by the finding that in a distinct group of 52 patients with progressive urothelial carcinoma 73% of the recurrent tumors displayed p53 accumulation.
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PMID:Predictive value of molecular alterations for the prognosis of urothelial carcinoma. 972 23

To further evaluate the role of the p53 gene in the development of colorectal carcinoma we examined by immunohistochemistry p53 protein expression in a series of 136 colorectal adenomas, 25 adenomas containing early invasive carcinoma (pT1) and 160 advanced adenocarcinomas (pT3-pT4). p53 overexpression was detected in 22% of adenomas, 64% of adenomas with invasive carcinoma and 60% of advanced adenocarcinomas. In colorectal adenomas p53 expression was related to tumour size (P = 0.0013), histologic type (P < 0.0001) and grade of dysplasia (P < 0.0001). Only 7.5% of adenomas with low grade dysplasia were found to be p53 positive, whereas 73.3% of adenomas with high grade dysplasia demonstrated p53 overexpression. Most p53 positive adenomas and adenomas with invasive carcinoma showed intratumoural heterogeneity of p53 immunoreactivity. Conversely advanced adenocarcinomas were always uniformly p53 positive or negative. Our data show that p53 protein overexpression occurs at the transition from low grade dysplasia to high grade dysplasia, indicating a likely role for the p53 gene in the conversion of benign adenoma to malignant carcinoma.
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PMID:[Expression of protein p53 in the adenoma-colorectal carcinoma sequence]. 979 94

Small adenocarcinomas of the colorectum showing no evidence of origin from an adenoma have been called de novo carcinomas, a name that implies an origin via a different molecular genetic mechanism than the usual colorectal carcinoma which develops from an adenoma. Using microsatellite analysis, 35 early (pT1) de novo and 36 pT1 ex-adenoma carcinomas were compared using 8 microsatellite loci at 6 different chromosomal loci (1p, 2p, 8p, 5q, 17p, and 18q) known or hypothesized to be important for colorectal carcinogenesis. The rate of loss of heterozygosity (LOH) at the 17p locus (near the p53 gene) was significantly higher in the de novo than in the ex-adenoma group (73 vs. 37%, P = 0.004). The rates of LOH at the other loci (including the APC and DCC genes) and the rate of MSI were not significantly different in the two groups. These results indicate that de novo carcinomas of the colorectum develop via a similar carcinogenetic pathway as conventional ex-adenoma carcinomas; however, their higher rate of LOH at 17p is evidence for a biologically more advanced lesion with more frequent p53 mutations, consistent with clinicopathological data indicating that de novo carcinomas are more aggressive than ex-adenoma carcinomas.
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PMID:Loss of heterozygosity and microsatellite instability in de novo versus ex-adenoma carcinomas of the colorectum. 984 87

Abnormal expression of the bcl-2 gene product (Bcl-2) has been found in a wide variety of tumors, including lung cancer. In the present study, a total of 116 tumor specimens from surgically resected non-small cell lung cancer (NSCLC) patients, that were previously studied for p53 protein expression, were analyzed with immunohistochemistry for Bcl-2 expression. Forty (34%) of 116 tumor specimens showed Bcl-2 expression, which was found to occur more frequently in males than females (p = 0.049) and to be associated with smoking (p = 0.047). Bcl-2 expression was more frequently observed in squamous cell carcinomas (27 of 51, 53%) than in adenocarcinomas (12 of 55, 22%; p = 0.002), and in pT1 tumors (11 of 13, 85%) than in pT2 and pT3 tumors (16 of 38, 42%) in squamous cell carcinomas (p = 0.01). Bcl-2 expression did not correlate either with p53 protein status. We compared Bcl-2 expression in primary tumors and metastatic tumors of regional lymph nodes. Of 11 cases with Bcl-2-negative primary tumors, 10 were Bcl-2-negative in metastatic tumors except 1 case. In contrast, of 10 cases with Bcl-2-positive primary tumors, 6 lost Bcl-2 expression in metastatic tumors, while the remaining 4 cases still showed Bcl-2 expression in metastatic tumors. In the 89 potentially curatively treated patients, those with Bcl-2-positive and Bcl-2-negative tumors did not show a significant difference in survival (5-year survival rates, 56 and 42%, respectively, p = 0.2 by the generalized Wilcoxon test). These data indicate that Bcl-2 expression is frequently observed in squamous cell carcinomas with early pT status, and that it does not predict prognosis of patients with NSCLC.
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PMID:Bcl-2 expression in non-small cell lung cancers: higher frequency of expression in squamous cell carcinomas with earlier pT status. 1020 83

The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.
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PMID:Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence. 1600 76

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade I, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21+/MDM2-/p53- and p21+/MDM2+/p53- observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21+/p53+ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins.
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PMID:Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21 phenotypes. 1071 38

Superficial transitional cell carcinoma of the bladder (STCCB) is a heterogeneous group of neoplasias with an unpredictable clinical course. In recent years many techniques have been used in order to predict the behaviour of these tumours at individual patient level. The aim of this study was to investigate in imprints from tumour biopsies the DNA ploidy and p53 protein expression in a group of 80 STCCB (pTa-pT1) patients in relation to histological grade and recurrence status. The DNA content was studied in Feulgen-stained imprints by the image analysis technique using a SAMBA 2005 analyser. In order to investigate p53 protein expression an avidin-extravidin immunocytochemical technique was used. According to our measurements a strong correlation was observed between recurrence status and DNA ploidy status (P < 0.001). No statistical difference was found in DNA ploidy status and grade of malignancy (P = 0.68). A statistically significant difference was found in p53 protein expression between recurrent and nonrecurrent tumours (P < 0.001). No statistically significant difference was found among tumours of grade I, grade II and grade III (P = 0.42). These results could provide useful information on the potential behaviour of STCCB.
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PMID:DNA ploidy and p53 protein expression in superficial transitional cell carcinoma of the bladder. 1077 9

The clinical value of p21WAF1/CIP1 in superficial bladder cancer remains controversial. To address the question, we examined the expression patterns of p21 and p53 gene products and compared for their significance in a total of 89 cases of superficial (pTa/pT1) bladder cancer. Over-expression of p21 was detected in 32 of 89 (36%) tumors. But, the expression status did not correlate with biological indicators or clinical outcome (p > 0.1, respectively). Factors predicting clinical outcome were multiplicity for tumor recurrence (p = 0.0002) or patient survival (p = 0.03), and the histological grading for disease progression (p = 0.02) or patient survival (p = 0.05). Taking into account the p53 status, a trend approaching better prognosis for p53+p21+ tumors was observed compared with that of p53+p21- bladder cancer (p = 0.08). Our data indicate that evaluation of p21 status does not provide better prognostic information compared with conventional biological indicators of superficial bladder cancer. Maintenance of p21 appears to abrogate the deleterious effects of p53 alterations in the tumorigenesis of human bladder.
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PMID:The clinical value of p21WAF1/CIP1 expression in superficial bladder cancer. 1081 Apr 17

Apoptosis is associated with caspase-mediated proteolysis of Type I (K18 and K19) cytokeratins. We previously showed a positive association between the levels of tissue polypeptide antigen (TPA), that recognizes cytokeratins K8, K18, and K19 fragments, and induced apoptosis in breast cancer cell lines. The aim of the present study was to evaluate the interrelationships between TPA, steroid receptors, and p53, and their joint prognostic role in node-negative breast cancer patients not treated with adjuvant therapies. Age and pT were also considered since they are known prognostic factors. Five hundred and ninety-nine cases with N- breast cancer were evaluated (median follow-up: 60 months). TPA was measured by an immunoradiometric assay and p53 by an immunochemiluminescent assay in tumor cytosol. Multiple correspondence analysis was used to study the associations among variables. Their prognostic role (univariate analysis) and their joint effect (multivariate analysis) on RFS were investigated with Cox regression models. TPA showed a direct association with ER and PgR. Higher p53 values were weakly associated to low values of ER, PgR, and TPA. Younger age was related to low and intermediate values of ER and PgR and to low p53 values, while older age was related to high values of ER. Multivariate analysis showed a significant prognostic impact for pT, age, ER, and TPA. Among the interactions considered clinically relevant, only that between ER and age was found. RFS estimated values were poorer in cases with lower than in those with higher TPA values, both in patients expected to have a poor (pT2, young age, low ER) and a better prognosis (pT1, older age, high ER). From the findings of the present study we can draw the following conclusions: The relationship of TPA with prognosis gives an additional contribution to pT, age, and steroid receptors in N- breast cancer; TPA may be considered the first marker of apoptosis measured with a fully standardized quantitative method in tumor cytosol and could be evaluated in prognostic indexes including markers related to different biological mechanisms.
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PMID:Quantitative measurement of soluble cytokeratin fragments in tissue cytosol of 599 node negative breast cancer patients: a prognostic marker possibly associated with apoptosis. 1083 91

We report a study of cell proliferative factors Ki67, PCNA and p53 oncoprotein in 55 patients with bladder tumors. Fifty-three of the patients were male and two were female, with a mean age of 56.6 and 68.5 years, respectively. These tumors were of transitional cell type in 97.9% of the cases. Staging was, respectively, pTis (4.76%), pTa (30.9%), pT1 (19.04%), pT2 (23.8%) and Pt3 (21.4%). Our study of proliferative nuclear markers Ki67 showed that cell proliferation increased in bladder tumors according to grade in the same stage. This variation was highlighted by our results for PCNA but was not verified for Ki67. However, these results revealed an increase of cell proliferation for a same grade (grade I and II) in different stages (pTa, pT1, pT2) for PCNA; this was not ascertained for Ki67. The study of p53 oncoprotein showed that detection of mutated p53 protein increased according to grade only for grades II and III and to stage only when moving from pTis to superficial tumors (pTa, pT1) and to deep tumors (pT2, pT3), thus individualizing two groups without significant variation within these groups. A variation according to grade in the same stage was noted only for stages pT1 and pT2. A variation for a same grade (grades II and III) was reported between stages pTa, pT1 and pT2. The combined study of Ki67, PCNA and p53 oncoprotein showed a prognostic correlation between these three markers in general.
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PMID:[Prognostic study of cell proliferative markers ki67, PCNA and p53 oncoprotein in bladder tumors]. 1099 43


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