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)

More than a decade ago an association between acute intermittent porphyria (AIP) and hepatocellular carcinoma (HCC) was reported, but still the cause of the increased prevalence is unknown. Paraffin sections of formalin-fixed HCC from 17 AIP patients were reexamined and also screened for relevant mutations using several methods. The tumor diagnosis was verified, and in several cases precirrhosis and cirrhosis were also found. The clinically founded AIP diagnosis was verified at the gene level in most cases, demonstrating the Norrland type of mutation, i.e., G(593)-to-A substitution in codon 198 of the porphobilinogen deaminase (PBGD) gene. The second allele was neither mutated nor missing, contradicting the possibility that the PBGD gene might function as a tumor suppressor gene. Subsequent sequencing showed that cases not cleaved by the restriction enzyme NheI lacked the specific Norrland mutation. In recent years, selective mutations at codons 249 and 166 of the p53 gene have been described in HCC associated with aflatoxin and hepatitis B virus. In our area, with low exposure to those agents, no mutations in codon 249 were found, and mutation in codon 166 was excluded in all tumors except one; no traces of hepatitis B DNA were observed. Nor did we find mutations in H-ras 12 or 61. Intrinsic aberrations in AIP, including reduced heme synthesis and endogenous oxidative damage to DNA, may incite carcinogenic mutations elsewhere in the genome of liver cells. The increased cell proliferation coupled to precirrhosis and cirrhosis perhaps represents promotion in the initiation-promotion sequence of hepatocarcinogenesis.
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PMID:Hepatocellular carcinoma in patients from northern Sweden with acute intermittent porphyria: morphology and mutations. 916 6

We used an immunohistochemical method to determine the concentrations of p53 and proliferating cell nuclear antigen (PCNA) to evaluate their usefulness as a predictor of malignancy and examined the relationship between PCNA and p53 in carcinomas of the extrahepatic bile duct (EHBD). Paraffin-embedded specimens from 46 patients were immunostained for PCNA and p53 using PC10 and DO7 monoclonal antibodies, respectively. The PCNA labeling index (LI) was closely associated with the stages of the tumor and depth of invasion (p < 0.05). The cumulative survival rate of patients with a low PCNA LI (LI < 47%) was found to be significantly better than that of patients with a high PCNA LI (LI > or = 47%) in all cases and patients with advanced cancer by univariate analysis (p < 0.05), but PCNA LI was not an independent prognostic factor in multivariate analysis. We detected p53 in 37% of the EHBD cancers. We also found that p53 positivity was not related to the percentage of PCNA-labelled cells or survival. The results suggest that PCNA immunoreactivity may be a useful predictor of malignancy in patients with EHBD carcinomas.
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PMID:Immunohistochemical detection of proliferating cell nuclear antigen and p53 expression in carcinoma of the extrahepatic bile duct. 926 Jun 3

Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2) gene product p16INK4A (p16) was analysed, following our previous study of p16. Forty-one percent of the benign, 50% of the LMP and most (71%) of the malignant tumours showed high pRB expression. High expression of pRB (>50% pRB-positive cells) significantly correlated with non-mucinous histological subtypes. Reduced pRB expression, substage and residual disease were significant predictors for poor prognosis in stage I patients. All the benign and most of the LMP (81%) tumours were in either the p53-negative or low p53-positive category, but nearly half of the malignant tumours had high p53 expression. High p53 accumulation was found in non-mucinous, high grade and late stage tumours. For well-differentiated carcinomas, high p53 expression was a predictor of poor prognosis. However, even though high p53 expression was not associated with histological subtype, stage or the presence of residual disease, high p53 expression was not an independent predictor when all clinical parameters were combined. For all ovarian cancers, a close correlation was found between high p53 and high p16 expression. The relationship between the expression of pRB and p16 depended on tumour stage. In stage I tumours, high pRB was associated with low p16 reactivity. On the other hand, most advanced tumours showed both high pRB and high p16 reactivity.
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PMID:Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer. 929 30

Recent studies have shown bcl-2 to be regulated by p53. Other studies have suggested an inverse relationship between p53 and bcl-2 protein expression in breast and colonic cancers and in a variety of subtypes of non-Hodgkin's lymphoma. This study investigates the relationship between bcl-2 and p53 protein expression and the correlation between these findings and the grade and cell type of follicular lymphomas according to the REAL classification. Paraffin-embedded nodal follicular lymphomas (n = 37) were subjected to bcl-2 and p53 immunohistochemistry on tissue sections using a three-step ABC system. Positive immunostaining for both oncoproteins was scored using a three-tiered scale: +, < 10 per cent cells; ++, 10-50 per cent cells; and ++(+), > 50 per cent cells (< 10 per cent was used as a cut-off to define negative tumours). Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1 = 6 per cent (1/16); grade 2 = 48 per cent (10/21); grade 3 = 100 per cent (6/6). Five cases comprised varying combinations of grades. This latter finding suggests a role for p53 mutation in the progression/transformation of follicular lymphoma. The mechanism, however, differs from that suggested in breast and colonic cancers, since an inverse relationship between bcl-2 and p53 was not demonstrated in the present study.
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PMID:bcl-2 and p53 protein expression in follicular lymphoma. 934 33

Paraffin-embedded hepatocellular carcinoma (HCC) samples were used to study point mutation of p53 gene at 249 codon in the exon 7 by polymerase chain reaction and gel electrophoresis under Hae III enzyme digestion. Fourteen primary tumor foci and 15 recurrent tumor foci from 11 patients were investigated. p53 gene point mutation was detected in 10 of 14 primary foci (71.4%), in 10 of 15 recurrent foci (66.7%) and in 10 of 12 multiple foci. The p53 genotype of the primary and recurrent tumor foci was the same in 5 patients but different in 6. The p53 genotype of the primary and recurrent tumor foci was identical in 5 patients with multiple tumor nodules. The results suggest that recurrent HCC was multi-centric in origin in 7 of the 11 patients but was mono-centric in the other 4 patients studied.
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PMID:[Analysis of cell origin of human hepatocellular carcinoma according to p53 gene mutation]. 938 69

Local and regional recurrence is the principal reason for treatment failure in squamous cell carcinoma (SCC) of the head and neck. The conventional method of evaluating surgical margins for cellular atypia does not always predict risk of local recurrence accurately. Immunostaining of surgical margins for tumor markers may provide a more precise evaluation of risk of local recurrence. Paraffin-embedded tissue blocks of surgical margins from 24 patients with oral cavity and oropharyngeal squamous cell carcinoma were immunostained for p53 protein. Fifty-eight percent of the patients had at least one margin stain positive for p53, including eight of ten patients whose SCC recurred locally. The sample odds ratio test predicted a 5.333 times higher chance of local recurrence with at least one p53 positive surgical margin. The implications of these results for patient management and further investigations will be discussed.
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PMID:p53 immunostaining of surgical margins as a predictor of local recurrence in squamous cell carcinoma of the oral cavity and oropharynx. 939 28

Most investigators agree that the most common antecedent of cancer in a breast is cancer in the opposite site. Thus, the present study focused on investigating the incidence of p53 gene abnormality in bilateral breast cancer and its correlation with proliferative activity and nuclear cytomorphology to demonstrate its significance in biological behavior and predicting the relatively small percentage of second tumors in the contralateral breast. Paraffin embedded tissue specimens obtained from 18 patients with bilateral primary breast cancer were studied. Ki-67 expression, a marker of tumor cell proliferation, was scored and p53 gene abnormalities were detected by avidin-biotin-peroxidase immunostaining. The mean nuclear volume of the tumor cells was assessed by a stereologic method. p53 gene abnormalities were detected in eight cases (44.4%). Seven cases (38.8%) exhibited strong Ki-67 immunopositivity, 10 cases (55.5%) exhibited weak Ki-67 immunopositivity and one case (5.5%) exhibited negative immunostaining. The mean nuclear volume was found to be 315.9 +/- 94.3 microm3 overall. The correlation between p53 mutations and the Ki-67 expression was statistically significant (P = 0.017, chi2-test), whereas the assessment of the mean nuclear volume also indicated significant correlation with p53 (P = 0.024, independent-samples t-test). However, we did not find any correlation between p53 mutation and either hormone receptor status or histological grade (P = 0.52, Fisher's test and P = 0.72, chi2-test, respectively). We have concluded that p53 gene abnormalities are detected in almost half of the bilateral breast cancers and are associated with high proliferative activity and mean nuclear volume. Although so far the number of patients is too small and the follow-up too short to determine the definitive prognostic value of p53 mutation, our preliminary results have indicated that it might be an indicator of a worse prognosis in bilateral breast cancer and a predictor of cancer in the contralateral breast.
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PMID:p53 mutations in bilateral breast carcinoma. Correlation with Ki-67 expression and the mean nuclear volume. 946 97

Core needle biopsies (CNB) are often used for the diagnosis of breast lesions. In some breast cancer patients, e.g., those treated with preoperative chemotherapy, the CNB specimen might be the only pretreatment tissue sample available for studies of prognostic and predictive markers. Our purpose was to evaluate whether marker studies performed on CNB specimens accurately reflect the marker status of the tumor. Immunostaining for five commonly used prognostic and predictive markers was performed on both CNB and subsequent excision specimens from 56 consecutive patients who had a CNB with carcinoma followed by excision of the tumor. None of the patients received radiotherapy or chemotherapy between the CNB and the excision. Paraffin sections of the CNB and excision specimens were immunostained for bcl-2, estrogen receptor (ER), c-erbB-2, and p53. These markers were scored as positive or negative. Microvessel density (MVD) was scored as a continuous variable on sections immunostained for Factor VIII-related antigen by calculating the average number of microvessels in three 224x fields of highest tumor vascularity ("hot spots"). Immunostaining results for bcl-2, ER, c-erbB-2, and p53 on the CNB and the corresponding excision specimens were 100% concordant. Although there was significant correlation between MVD on the CNB specimens and the corresponding excisions (r = 0.507, P = 0.0002), the mean MVD on the CNB and corresponding excision specimens differed by more than 10% in 85.7% of cases, with differences ranging from 4.3 to 233.3%. MVD was higher in the CNB than in the excision specimens in 30 (61.2%) of 49 cases. In conclusion, in all of the cases studied, accurate results for the dichotomously scored markers bcl-2, ER, c-erbB-2, and p53 were obtained on CNB specimens. In contrast, in most cases, MVD, which was scored as a continuous variable, could not be reliably assessed on the CNB specimen.
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PMID:Do prognostic marker studies on core needle biopsy specimens of breast carcinoma accurately reflect the marker status of the tumor? 952 72

Apocrine phenotype is observed in a spectrum of breast epithelial lesions spanning from benign metaplasias to apocrine carcinoma. Apocrine metaplasia is a common finding in fibrocystic change of the female breast. In situ and invasive apocrine carcinomas are rare variants of ductal carcinoma. All breast apocrine lesions were shown to be associated with increased androgen hormones metabolism. We have evaluated 10 cases of apocrine metaplasia, 3 cases of in situ apocrine carcinoma and 10 cases of invasive apocrine carcinomas using immunostaining method for steroid hormone receptors (estrogen, progesterone, androgen), p53, bcl-2 and BRST-2. Paraffin embedded tissue and avidin-biotin peroxidase complex system were used. Androgen receptor (AR) expression is consistently increased in all cases of apocrine metaplasia when compared with surrounding normal, non-apocrine breast epithelium. This androgen receptor over-expression is accompanied by the loss of immuno-detectable estrogen and progesterone receptor, and also the loss of bcl-2. An identical pattern of immuno-reactivity is seen in in situ apocrine carcinomas, but it is observed with less frequency in invasive apocrine carcinomas, which only infrequently express AR as the only steroid hormone receptor.
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PMID:Immunohistochemical analysis of apocrine breast lesions. Consistent over-expression of androgen receptor accompanied by the loss of estrogen and progesterone receptors in apocrine metaplasia and apocrine carcinoma in situ. 952 7

The p53 gene is well known as a tumour suppressor gene. In addition, the mutated p53 gene is detected in a variety of human cancers including lung cancer, and is considered as an oncogene. Lung cancer is also frequently associated with interstitial lung diseases. Therefore, it may be possible to hypothesize that there might be some abnormality of p53 gene in interstitial lung diseases. This work examined the relationship between the p53 protein and gene in lung tissues of 28 patients with interstitial lung diseases. Among 28 patients, 13 cases were pathologically diagnosed to have usual interstitial pneumonia (UIP), 12 cases were diagnosed as having collagen vascular lung diseases, and three cases were diagnosed to have a non-specific interstitial pneumonia. Twenty-three tissue samples were obtained by open lung biopsy and five samples were taken by autopsy. Paraffin-embedded tissues were treated by microwave, and stained with an anti-p53 antibody (DO7) by the Avidin-Biotin-Peroxidase (ABC) method. In selected patients, mutations in exons 5-8 of the p53 gene were also examined by single-strand conformation polymorphism (SSCP) analysis and DNA sequence. In addition, the presence of anti-p53 antibodies in patients' sera was screened for by ELISA. Fifteen samples (53.6%) revealed overexpression of the p53 protein in the nuclei of alveolar epithelial cells. However, SSCP or sequence analysis, which was performed in 13 tissues, showed no mutations in exons 5-8 of the p53 gene. In conclusion, p53 proteins were overexpressed in interstitial lung diseases, and the expressed p53 protein was considered to be wild-type. This wild-type p53 protein may play a role in blocking the transformation of proliferative epithelial cells.
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PMID:Overexpression of p53 protein in interstitial lung diseases. 961 10


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