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)

The proliferative activity in 35 cases of breast carcinoma was evaluated by bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) and was compared with benign breast lesion. Overexpression of p53 and c-erbB-2 oncoprotein, presence of estrogen receptor (ER) and cellular localization of multidrug resistance gene product P-glycoprotein (P-gp) were immunohistochemically examined to investigate the relation with the proliferative activity and clinicopathologic characteristics. The mean BrdU labeling index (LI) was 12.6% and PCNA labeling rate (LR) was 33.5% in breast carcinomas, and good correlation was found between them. The proliferative activity of breast carcinomas was significantly higher than that of benign lesions. The BrdU LI correlated positively with tumor size, histologic grade, TNM stage and p53 immunoreactivity, and negatively with the presence of ER. PCNA LR correlated with histologic grade and expression of p53. p53 protein was demonstrated in 43% of the breast carcinomas and correlated with proliferative activity. The extent of p53 immunoreactivity on carcinoma cells was also related to BrdU LI. c-erbB-2 oncoprotein was demonstrated in 51% of the breast carcinomas and correlated with histologic grade. ER was found in 34% of the breast carcinomas and correlated negatively with histologic grade, lymph node metastasis and TNM stage. P-gp was observed in 49% of the breast carcinomas and no correlation was found with clinicopathologic characteristics. None of the benign lesions expressed p53 protein, c-erbB-2 oncoprotein and P-gp. BrdU is a reliable standard and a more useful tool for the evaluation of proliferative activity of breast tumors. High proliferative activity, overexpression of p53 protein and the absence of ER are considered as a high grade malignancy of breast carcinoma. Expression of c-erbB-2 oncoprotein and P-gp may be related to malignant transformation of breast tumors.
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PMID:Proliferative activity in breast carcinoma evaluated by BrdU and PCNA. Correlation with expression of p53, c-erbB-2, estrogen receptor and P-glycoprotein. 882 14

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.
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PMID:Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG). 895 93

p53 protein accumulation, thought to be caused by p53 gene mutation, is closely related to poor prognosis of patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (SCC) is also strongly suspected to depend on the p53 tumor suppressor gene. Formalin-fixed, paraffin-embedded sections were taken from 25 patients who underwent esophagectomy for SCC. Fourteen patients had no preoperative therapy (control group), while the other 11 patients received preoperative radiotherapy (radiation group). There was no difference in pathological TNM classification between the two groups. These sections were examined by immunostaining with monoclonal antibody PAb 1801 to determine the accumulation of p53 protein, and apoptotic frequency was determined by TdT mediated dUTP-biotin nick end-labeling (TUNEL). In the control group, well to moderately differentiated cases showed a significantly higher AI (apoptotic index which is the number of apoptotic cells among 1000 cancer cells. %0) (51.7+/-83.4) than poorly differentiated cases (AI=1.3+/-1.0) (P<0.05). Similar results were obtained in the radiation group. The former group included 4 cases of p53 grade 4 (p53 protein detected in over 70% of the tumor cells), and the latter included 2. Few apoptotic cells were observed in any of 6 tumor tissues. In each patient, tumor cells with accumulated p53 protein were very rare to be apoptotic. On the other hand, apoptosis was observed in tumor cells without p53 protein accumulation. Spontaneous apoptosis in esophageal SCC can be induced more easily in differentiated than in poorly differentiated cases. This tendency may be enhanced by preoperative radiotherapy. Extensive p53 protein may suppress apoptotic induction in esophageal squamous cell carcinomas.
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PMID:Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing extensive p53 protein. 900 43

As chromosomes 2p and 3p are frequent targets for genomic instability in lung cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by polymerase chain reaction (PCR) assay replication errors (RER) and loss of heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64 paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic sequencing, as well as their relationship with clinical outcome. Forty-two of the 64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected in 23 tumours (36%). Among patients with stage I disease, the 5-year survival rate was 80% in those whose tumours had no evidence of RER and 26% in those with RER (P = 0.005). No correlation was established between RER phenotype and LOH, K-ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for all other evaluated factors, including p53, K-ras, LOH, histological type, tumour differentiation and TNM stage, suggesting that microsatellite instability on chromosomes 2p and 3p may play a role in NSCLC progression through a different pathway from the traditional tumour mechanisms of oncogene activation and/or tumour-suppressor gene inactivation.
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PMID:Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer. 901 24

Blood normal and tumor tissue samples of 23 patients with sporadic colorectal tumors were screened for DNA alterations in the tumor relevant genes APC, K-ras, DCC and p53. Six different microsatellite regions were analyzed for instability by a new developed non-radioactive method. Somatic DNA alterations were found in 17 tumor samples: 13 carried single or multiple changes in single genes; six carried alterations in microsatellites; two tumors showed tumor suppressor gene mutations in addition to microsatellite changes. We found no indications of correlations between current genetic models of colorectal tumor progression and the established TNM system for histopathological tumor classification.
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PMID:DNA alterations in sporadic colorectal tumors do not correlate with tumor staging diagnosed by the TNM system. 902 Sep 16

The p53 gene is known as an anti-oncogene that manifests its function by controlling the cell cycle and is responsible for apoptosis of cells with unrepaired DNA. An accelerated p53 protein synthesis is the first response of a cell following DNA damage. However, mutations of the p53 gene can disturb protein synthesis or may be responsible for synthesis of a changed protein unable to control the cell cycle. Laryngeal tissue specimens from 120 patients were tested by immunohistopathological staining to detect mutated wild-type p53 protein. It was found that p53-positive specimens correlated with TNM staging and histopathological grading. Another indication of entering the cell cycle and undertaking an active proliferation by laryngeal cells was shown by detection of proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen, which appeared in proliferating cells (late G1, S-G2 and M phase), but was absent in resting cells. Scoring of the staining for p53 protein, PCNA and Ki67 correlated with each other. DNA from 40 specimens was then isolated, amplified by polymerase chain reaction and analysed by single-strand conformation polymorphism and DNA sequencing for mutation in the p53 gene. Fifteen DNA samples were found to be positive, while mutations were detected in exons 5-8 in 13 samples. The majority of mutations were found in tissue specimens from T3 and T4 tumors. A possible explanation is almost half was attributable to genotoxic effects of tobacco smoking. Changes in the p53 gene and its products may also reflect early changes in laryngeal carcinogenesis and be of prognostic value.
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PMID:Alteration of p53 gene structure and function in laryngeal squamous cell cancer. 906 48

TNM staging of oesophageal cancer provides significant prognostic information but its clinical impact is limited as many patients present with advanced disease (i.e. T3N1). Additional prognostic markers may help separate those with 'good' and 'bad' prognosis tumours and so help with decisions such as selection for adjuvant therapy. p53 and c-erbB-2 overexpression may correlate with poor prognosis in oesophageal cancer, but this is uncertain. This study aimed to investigate the value of these biomarkers as prognostic indicators in resected oesophageal cancer. Two hundred and five oesophageal tumours (127 adenocarcinoma, 78 squamous) resected by a single surgeon between June 1979 and January 1991 were investigated for p53 and c-erbB-2 overexpression using DO-7 and CB-11 immunohistochemistry. Patient survival was analysed by Kaplan-Meir life tables. Median survival was 61 weeks (range: 5-747) and survival diminished significantly with increasing UICC stage (P < 0.0001). Sixty-eight per cent of squamous tumours and 66% of adenocarcinomas overexpressed p53 but there was no statistically significant correlation with prognosis. Twenty-six per cent of squamous tumours and 23% of adenocarcinomas overexpressed c-erbB-2, but again this did not correlate with survival. p53 and c-erbB-2 are commonly overexpressed in oesophageal cancer but do not appear to be related to prognosis in this large series of resected oesophageal cancers and other candidate biomarkers must be sought.
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PMID:Immunohistochemical detection of p53 and c-erbB-2 in oesophageal carcinoma; no correlation with prognosis. 906 44

The proliferative activity of 30 cases of non-treated invasive ductal breast carcinoma was evaluated by bromodeoxyuridine (BrdU), proliferation marker (MIB-1) and proliferating cell nuclear antigen (PCNA), and the relation between these proliferation markers and histological subtype and histological grade were investigated. In addition, the association of these proliferation markers with overexpression of p53 protein, c-erbB-2 oncoprotein, estrogen receptor (ER) status and clinicopathologic findings were also examined. The BrdU labeling index (LI), MIB-1 score and PCNA labeling rate (LR) correlated with the histological grade. However, there was no statistical difference in proliferative activity among the histological subtypes. A linear strong correlation was demonstrated between BrdU LI and MIB-1 score (r = 0.732). Significant correlation was also found between BrdU LI and PCNA LR (r = 0.446); however, the relation between MIB-1 score and PCNA LR was weak. BrdU LI and MIB-1 score correlated positively with tumor size, TNM stage and overexpression of p53, and negatively with the presence of ER. PCNA LR correlated only with p53. These results indicate that MIB-1 is closely associated with BrdU in clinicopathologic findings and is a more useful tool for evaluating cell proliferation than PCNA. However, it will be necessary to consider the clinical significance of MIB-1 immunohistochemistry cautiously until further widespread clinical and pathological studies are performed.
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PMID:Proliferation marker MIB-1 correlates well with proliferative activity evaluated by BrdU in breast cancer: an immunohistochemical study including correlation with PCNA, p53, c-erbB-2 and estrogen receptor status. 911 Mar 47

We have performed immunohistochemical staining for p53 and c-erbB-2 on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months. All of them had received postoperative chemoradiation therapy. We have analyzed the association of these factors with epidemiologic risk factors, histopathologic features and hormonal receptor status and the influence on prognosis. Our results indicate that the expression of c-erbB-2 protein defines a group of node-negative patients with poor prognosis. The overexpression of c-erbB-2 has shown a significant association with estrogen receptor status (those tumors expressing c-erbB-2 are usually estrogen receptor negative), presence of fibrosis and lymphoplasmacytoid infiltrates. P53 expression has shown no relation either with prognosis or with any other histopathologic or clinical feature. The only factors with prognostic influence in our series have been tumor size, the presence of node metastases, TNM stage and the prognostic morphometric index (Baak's index), apart from c-erbB-2 in node-negative patients. However, only the TNM stage showed an independent association with prognosis after a multivariate analysis. In summary, in our experience the expression of p53 protein has no prognostic influence on breast carcinoma, and TNM stage remains to be as the most powerful prognostic factor in these patients.
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PMID:Immunohistochemical expression of p53 and c-erbB-2 in breast carcinoma: relation with epidemiologic factors, histologic features and prognosis. 922 51

475 patients with carcinoma at different sites (141 colon-rectum; 102 breast; 50 stomach; 48 kidney; 46 head and neck; 41 bladder; 47 other sites) submitted to surgery have been analyzed after histopathological staging and grading, by flow cytometry (monoparametric DNA content analysis) and immunohistochemistry (p53, c-erbB-2, and PCNA expression). In breast cancer patients the presence of receptors for estrogen (ER) and progesterone (PGR) has also been determined. Flow cytometry-derived parameters were DNA ploidy, fraction of cells in S-phase (SPF), and DNA content heterogeneity (multi-clonal stem cell lines with different DNA index and/or more than one subpopulations with different ploidy levels in different samples from the same tumor). Correlations of the results obtained by the different techniques have been attempted by the non-parametric Spearman's rank correlation approach. Significant associations (P < 0.05) were found between the histopathological, immunohistochemical and flow cytometric parameters considered in some anatomical regions, such as stomach (p53 vs DNA content aneuploidy and vs heterogeneity), colon-rectum (TNM vs p53 and vs heterogeneity), bladder (grading vs DNA content aneuploidy and vs heterogeneity). Tumor heterogeneity proved to be dependent on the number of tumor samples taken. The results of this preliminary assessment will subsequently be compared with the data obtained from a currently ongoing follow-up survey.
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PMID:Flow cytometric and immunohistochemical correlations in high incidence human solid tumors. 926 90


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