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)

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

Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (> or = 5% of cells positive) and cyclin D1 positive (> or = 10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P < 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P = 0.001), WHO grade (P = 0.006), MIB-1 score (P = 0.014), p53 expression (P = 0.001), and bcl-2 (P = 0.011) immunoreactivity. In univariate analysis, T category (P = 0.0001), WHO grade (P < 0.0001), MIB-1 score (P < 0.0001), bcl-2 (P = 0.0092), p53 (P = 0.0016) and p21WAF1/CIP1 (P = 0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P = 0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P = 0.03), whereas tumor grade (P = 0.002) and cyclin D1 expression (P = 0.04) were independent predictors of tumor recurrence. Only the WHO grade (P = 0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.
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PMID:Evaluation of p21WAF1/CIP1 and cyclin D1 expression in the progression of superficial bladder cancer. Finbladder Group. 1112 4

We investigated the expression of oncogenes p53, c-erbB-2, and bcl-2 and cell proliferative activity in 62 newly diagnosed superficial pTa papillary bladder tumors. Based on the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications, 19 were urothelial neoplasias of low malignant potential (LMP) and 43 low-grade (grade 1) papillary carcinomas. All the patients underwent transurethral resection and were followed up to 97 months; 42 had recurrences. Initial biopsies were tested for p53, c-erbB-2, and bcl-2 proteins using DO7, CB11, and bcl-2 124 monoclonal antibodies. Cell proliferation was assessed by MIB-1 mAb and mitotic count. LMP had significantly lower MIB-1 (p = 0.002) and p53 immunopositivity (p = 0.03), mitotic count (p = 0.006), and recurrence rates (p = 0.04) than did grade 1 cases, whereas no difference was observed for c-erbB-2 and bcl-2 expression. The median disease-free survival for LMP was 76 months but only 15 months for grade 1 cases (p = 0.002). Although the cohort is small, the results indicate that the distinction between LMP and low-grade (grade 1) papillary urothelial neoplasias, as proposed by the 1998 WHO/ISUP and 1999 WHO classifications, reflects different biologic activity and clinical behavior; however, a long-term follow-up is advisable also for patients with LMP.
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PMID:Biologic differences between noninvasive papillary urothelial neoplasms of low malignant potential and low-grade (grade 1) papillary carcinomas of the bladder. 1171 43

Molecular markers are needed for better distinguishing of non-invasive papillary (pTa) and minimally invasive (pT1) bladder carcinomas and for identifying individual tumors with a high risk of recurrence or disease progression. First aim of our study was to evaluate TP53 microsatellite and mutation analysis as an effective concept for the characterization of superficial bladder tumors with different biological aggressiveness. Mutation screening in the TP53 hot spot region was performed in 55 microdissected superficial bladder tumor samples by direct genomic sequencing. PCR based LOH analysis was done with two markers at 17p13. Second, there is considerable interest in the development of non-invasive techniques that would detect recurrent bladder neoplasia. In order to evaluate TP53 alterations as a potential marker for a non-invasive diagnosis of recurrences or residuals and to determine whether tumor-specific DNA exhibiting LOH or sequences harbouring a mutation, can be detected in body fluids, mutation screening was performed in urine, plasma and serum of patients with a mutated primary tumor. LOH analysis with two markers at 17p was done in the corresponding urine and blood samples of 31 primary tumors. As seen from our results, TP53 inactivation by mutation seems to characterize higher malignant superficial bladder tumors which tend to recur and in which the probability is higher that the rezidives progress to muscle invasive growth pattern. Only in 2/8 cases, the TP53 mutation from the primary tumor could be re-detected in patients urine and blood. 17p microsatellite changes with at least one marker were found in 30/31 body fluids of the tumor patients (97%). Correlating the 17p status found in body fluids to the status of the primary tumor, the concordance is only about 52%. We conclude that TP53 genotyping as a non-invasive diagnostic tool in outpatient samples is of limited value for clinical practice.
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PMID:TP53 alterations as a potential diagnostic marker in superficial bladder carcinoma and in patients serum, plasma and urine samples. 1174 49

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

In predicting the aggressive behavior of bladder tumors, the histopathological characteristics of grade and invasive stage are of principal importance. However, for predicting tumor recurrence and progression, these are sufficient only to a limited extent, particularly in the case of superficial (pTa and pT1) urothelial cell carcinomas. New prognostic factors are therefore needed to avoid either insufficient or excessive treatment. In this retrospective study, we investigated the prognostic value of the p53 and Ki-67 immunoreactivity indices. The present study included 118 superficial urinary bladder tumors consisting of 58 recurrent and 60 non-recurrent cases. Twenty of the recurrent tumors progressed into a higher grade and/or invasive stage. Paraffin immunohistochemical analysis was carried out using anti-p53 and anti-Ki-67 antibodies on the initial tumor tissues. We concluded that there is a highly significant relationship between the p53 and Ki-67 immunoreactivities and the histological grade and pathological stage of the tumors (P < 0.0001). We observed a significant relationship between the presence of recurrence and progression and the p53 immunoreactivity index (P < 0.01 and P = 0.017, respectively) and Ki-67 immunoreactivity index (P < 0.0001 and P = 0.046, respectively). Positivity for p53 and Ki-67 can demonstrate the risk of recurrence (p53: sensitivity = 76%, specificity = 58%; Ki-67: sensitivity = 86%, specificity = 48%) and progression (p53: sensitivity = 80%, specificity = 46%; Ki-67: sensitivity = 85%, specificity = 36%; ). We believe that both of these immunohistochemical markers can be considered valuable in addition to classical histopathological prognostic parameters for predicting recurrence and progression risks.
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PMID:Impact of p53 and Ki-67 in predicting recurrence and progression of superficial (pTa and pT1) urothelial cell carcinomas of urinary bladder. 1216 5

Carcinoma in situ (CIS) of the urinary bladder is a flat, aggressive lesion and may be the most common precursor of invasive bladder cancer. Although chromosome 9 alterations are among the earliest and most prevalent genetic alterations in bladder cancer, discrepancy exists about the frequency of chromosome 9 losses in CIS. We analyzed 22 patients with CIS of the bladder (15 patients with isolated CIS, 7 patients combined with synchronous pTa or pT1 carcinomas) for gains and losses of chromosome (peri)centromere loci 1q12, 7p11-q11, 9p11-q12, and 9p21 harboring the INK4A/ARF locus (p16(INK4A)/p14(ARF)) and INK4B (p15(INK4B)) by multiple-target fluorescence in situ hybridization, and for p53 protein accumulation by immunohistochemistry. In 15 of 20 (75%) CIS lesions analyzed p53 overexpression was detected, whereas aneusomy for chromosomes 1 and 7 was identified in 20 of 22 (91%) CIS. In 13 of 22 (60%) CIS cases analyzed, 12 of which were not associated with a synchronous pTa or pT1 carcinoma, no numerical losses for chromosome 9 (p11-q12 and 9p21) were detected as compared with chromosomes 1 and 7. Furthermore 6 of 12 (50%) patients showed a metachronous invasive carcinoma within 2 years. In the remaining nine biopsies CIS lesions (40%) were recognized that showed losses of chromosome 9p11-q12 and 9p21, six of these were associated with a synchronous pTa or pT1 carcinoma. Three of these carcinomas were pTa and exhibited loss of 9q12 as well as a homozygous deletion of 9p21. The others were invasive carcinomas in which CIS lesions were also recognized that showed no numerical loss of chromosome 9, but did show an accumulation of p53. In conclusion our data demonstrate that predominantly isolated CIS lesions contained cells with no specific loss of chromosome 9, as opposed to CIS lesions with synchronous carcinomas that showed evidence of chromosome 9 loss. Furthermore our data strengthen the proposition that p53 mutations (p53 overexpression) precede loss of chromosomes 9 and 9p21 in CIS as precursor for invasive bladder cancer, as opposed to noninvasive carcinomas where chromosome 9 (9p11-q12) losses are early and frequently combined with homozygous deletions of 9p21.
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PMID:Identification of chromosome 9 alterations and p53 accumulation in isolated carcinoma in situ of the urinary bladder versus carcinoma in situ associated with carcinoma. 1236 85

Approximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki-67 immunoexpression in low-grade (GI-II) USPC in order to predict the potential outcome of these tumors. P53 and Ki-67 immunoexpression were studied in function of recurrence-free and progression-free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki-67 index (>/=18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression-free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki-67 index into the risk model, single pTa/T1-GI Ki-67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1-G1 with a high risk of recurrence and progression. Ki-67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low-grade USPC, the accuracy of the prognostic discrimination is enhanced.
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PMID:Ki-67 index enhances the prognostic accuracy of the urothelial superficial bladder carcinoma risk group classification. 1267 90

Approximately 10% of patients with superficial bladder cancer (pTa/pT1) recur with life-threatening muscle-invasive disease. Identification of these patients has been a major goal of bladder cancer research. In 1994, it was suggested that p53 immunostaining could identify the cancers that would progress and it was proposed that tumours that stain for p53 should be treated aggressively with radiotherapy or cystectomy. Despite the hundreds of studies published since on the relationship between p53 and progression in superficial bladder cancer, the clinical utility of p53 immunostaining has not been resolved because of limitations concerning the numbers of patients and the length of follow-up. This study set out to overcome these limitations by using tissue from a large multicentre trial that recruited 502 patients with a median follow-up of 10 years. Each of 34 patients that had progressed with >/= pT2 disease or had distant metastases or had died from bladder cancer was compared with one or two matched controls. Sections were stained with a mouse monoclonal antibody to p53, pAb1801. In agreement with many of the earlier studies, p53 immunostaining had prognostic significance. The adjusted hazard ratio for time to progression for the pAb1801-positive versus negative group was 2.5, with 95% confidence intervals of 1.05-5.98 (p = 0.039). The other major risk factor that is associated with progression of superficial bladder cancer is pT1G3 disease. Of the 42 pT1G3 cancers, 14 (33%) progressed. The proportion of cancers with p53 staining that progressed was similar to the proportion of pT1G3 cancers that progressed, but neither the sensitivity nor the specificity of association of p53 staining with progression is sufficient to recommend cystectomy in individual patients.
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PMID:Can p53 staining be used to identify patients with aggressive superficial bladder cancer? 1269 44

FGFR3 and TP53 mutations are frequent in superficial papillary and invasive disease, respectively. We used denaturing high-performance liquid chromatography and sequencing to screen for FGFR3 and TP53 mutations in 81 newly diagnosed urothelial cell carcinomas. Tumors were classified as follows: 31 pTa, 1 carcinoma in situ, 30 pT1, and 19 pT2-T4. Tumor grades were as follows: 10 G1, 29 G2, and 42 G3. FGFR3 mutations were associated with low-stage (P < 0.0001), low-grade (P < 0.008) tumors, whereas TP53 mutations were associated with high-stage (P < 0.003), high-grade (P < 0.02) tumors. Mutations in these two genes were almost mutually exclusive. Our results suggest that FGFR3 and TP53 mutations define separate pathways at initial diagnosis of urothelial cell carcinoma.
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PMID:FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder. 1467 61


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