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)

p53 mutation and p53 protein overexpression are common findings in ovarian carcinomas. In order to evaluate the prognostic significance of the p53 status and its role in metastasis, we examined 104 ovarian carcinomas, among them 83 cases with follow-up data, and 40 pairs of primary tumors and metastases, by p53 immunohistochemistry and temperature-gradient gel electrophoresis. Comparison of primary tumors and their metastases revealed identical results in 88%-90% of the cases, indicating that, in most cases, mutant p53 occurs prior to metastatic spread and remains clonally conserved. With respect to all tumors, moderate/high p53 expression was significantly more prevalent in serous-papillary types, carcinomas with high grade, and high Ki67 scores, but was not associated with age, stage, or hormone receptor status. Kaplan-Meier analysis of 83 cases, followed-up for 9-96 months, demonstrated that moderate/high p53 overexpression in the group of 66 stage T3/M1 tumors was associated significantly (P = 0.0028 and P = 0.0105) with shorter overall and recurrence-free survival. Multivariate analysis revealed that advanced clinical stage and p53 positivity were the only independent predictive variables. No significance was seen in regard to second-look results and outcome of 50 patients receiving platinum-based chemotherapy. These observations show that p52 immunohistochemistry is an independent prognostic indicator at the given cut-off level, but does not reliably predict chemotherapy response.
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PMID:p53 is a persistent and predictive marker in advanced ovarian carcinomas: multivariate analysis including comparison with Ki67 immunoreactivity. 934 99

Thyroid hormone receptor (T3R) is a member of the steroid hormone receptor gene family of nuclear hormone receptors. In most cells T3R activates gene expression only in the presence of its ligand, L-triiodothyronine (T3). However, in certain cell types (e.g., GH4C1 cells) expression of T3R leads to hormone-independent constitutive activation. This activation by unliganded T3R occurs with a variety of gene promoters and appears to be independent of the binding of T3R to specific thyroid hormone response elements (TREs). Previous studies indicate that this constitutive activation results from the titration of an inhibitor of transcription. Since the tumor suppresser p53 is capable of repressing a wide variety of gene promoters, we considered the possibility that the inhibitor is p53. Evidence to support this comes from studies indicating that expression of p53 blocks T3R-mediated constitutive activation in GH4C1 cells. In contrast with hormone-independent activation by T3R, p53 had little or no effect on T3-dependent stimulation which requires TREs. In addition, p53 mutants which oligomerize with wild-type p53 and interfere with its function also increase promoter activity. This enhancement is of similar magnitude to but is not additive with the stimulation mediated by unliganded T3R, suggesting that they target the same factor. Since p53 mutants are known to target wild-type p53 in the cell, this suggests that T3R also interacts with p53 in vivo and that endogenous levels of p53 act to suppress promoter activity. Evidence supporting both functional and physical interactions of T3R and p53 in the cell is presented. The DNA binding domain (DBD) of T3R is important in mediating constitutive activation, and the receptor DBD appears to functionally interact with the N terminus of p53 in the cell. In vitro binding studies indicate that the T3R DBD is important for interaction of T3R with p53 and that this interaction is reduced by T3. These findings are consistent with the in vivo studies indicating that p53 blocks constitutive activation but not ligand-dependent stimulation. These studies provide insight into mechanisms by which unliganded nuclear hormone receptors can modulate gene expression and may provide an explanation for the mechanism of action of the v-erbA oncoprotein, a retroviral homolog of chicken T3R alpha.
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PMID:Constitutive activation of gene expression by thyroid hormone receptor results from reversal of p53-mediated repression. 937 52

The expression of Bcl-2, a suppressor of apoptotic cell death, was investigated in 52 invasive carcinomas of the breast using reverse transcription-polymerase chain reaction and immunohistochemical methods. After consideration of both sets of results, 42 tumors (80.8%) were confirmed to be positive (Bcl-2(+)) and 10 (19.2%) were judged negative (Bcl-2(-)) for Bcl-2 expression. Related factors (p53 protein accumulation, hormone receptor status and apoptotic cell index) were also examined using immunohistochemical and in situ end-labeling methods to elucidate their correlations with Bcl-2 expression. Bcl-2 expression correlated significantly with the hormone receptor status, whereas it showed significant inverse correlations with p53 accumulation and the apoptotic index. It was concluded that estrogen and mutant p53 are related to the regulation of Bcl-2 expression and that the ability to prevent tumor cell death due to Bcl-2 can be developed by breast cancers.
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PMID:Expression of Bcl-2 in human breast cancer: correlation between hormone receptor status, p53 protein accumulation and DNA strand breaks associated with apoptosis. 941 34

We examined the association between mutation of the p53 gene and survival in a large cohort of breast cancer patients. Using a rapid, non-isotopic single-strand conformation polymorphism (SSCP) method we screened for mutations in exons 4-10 of the p53 gene in 375 primary breast cancers from patients with a median follow-up of 57 months. Mutations were found in 19% of tumours. Statistically significant associations were found between p53 mutation and histological grade, hormone receptor status, ploidy and S-phase fraction. No association was found between p53 mutation and axillary lymph node involvement, histological type, tumour size, vascular invasion or patient age. In univariate survival analysis, p53 mutation was strongly associated with poor prognosis. This was maintained in the lymph node-negative and hormone receptor-positive patient subgroups. In multivariate analysis, p53 mutation was associated with poor survival independent of lymph node status, estrogen receptor status and S-phase fraction. Our results demonstrate the feasibility of using a rapid and simple polymerase chain reaction-SSCP screening procedure to detect p53 gene mutation in breast cancer for the provision of prognostic information.
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PMID:Detection of p53 gene mutation by rapid PCR-SSCP and its association with poor survival in breast cancer. 942 63

The accumulation of p53 protein was evaluated by a novel luminometric immunoassay (LIA) in cytosol samples from a series of 245 primary breast cancers. The cytosolic p53 content was not related to nodal status or hormone receptor status, but it was significantly and directly associated with tumor size and cell proliferation. A matched comparison between immunohistochemistry (IHC) and LIA results of individual tumors showed a significant association, albeit with a correlation coefficient of only 0.41. The agreement of results from the two assays was higher in node-positive, estrogen-receptor-negative and rapidly proliferating tumors than in the complementary subgroups. Overall, there was a significant trend in favor of an increase in p53 levels as determined by LIA with the increase in p53-positive cells shown by IHC. However, taking IHC detection as a reference, the sensitivity of the LIA was better for negative (86%) than for positive (61%) values. Based on these findings, a comparative assessment of the clinical relevance of LIA versus IHC results has to be recommended.
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PMID:P53 accumulation in primary breast cancer: a comparison between immunohistochemistry and a novel luminometric immunoassay. 942 78

Mutations of the p53 gene appear to be one of the most common abnormalities in human cancer. Although many studies have been published about p53 alterations in breast cancer, data on molecular biological detection of p53 mutations in in situ lesions are still rare, and the implications for breast cancerogenesis are unclear. Tissue samples from 83 patients with different stages of breast cancer and from 13 patients with benign breast lesions were screened for p53 gene mutations by polymerase chain reaction (PCR) followed by temperature-gradient gel electrophoresis (TGGE). p53 protein accumulation was analysed by immunohistochemistry (IHC). Samples were gained from fresh-frozen tissue, scrapings, or paraffin embedded tissue. Additionally, 23 pairs of primary tumours and corresponding lymph nodes were examined. p53 gene aberrations were found in 55.7% of the infiltrating carcinomas, in 31.5% of the ductal carcinomas in situ (DCIS) and in one atypical ductal hyperplasia. A positive correlation was seen with high-grade tumours and with comedo. There was no statistically significant relationship with respect to age, menopausal status, tumour size, hormone receptor status or lymphatic invasion. Concordance between TGGE and IHC was seen in only 63% of the cases analysed. However, with regard to p53 mutation screening by TGGE, a high significance (P = 0.0008) was seen between standard tissue extraction and our scrape preparation technique. Among 8 pairs of primary tumours and their corresponding lymph node metastases, only 3 harbored identical p53 mutations in the same exon, while in 5 cases with mutant p53 in the primaries, no mutation was seen in the lymph node. Our data indicate that p53 mutations are frequent in breast tumours associated with unfavorable prognosis, including high-grade or the comedo histotype. There is evidence that p53 gene alterations occur early in breast cancerogenesis, as mutations were detected not only in in situ carcinomas but also in atypical ductal hyperplasia.
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PMID:Molecular and immunohistochemical analysis of p53 mutations in scrapings and tissue from preinvasive and invasive breast cancer. 942 25

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

The role of p53 in modulating apoptosis has suggested that it may affect efficacy of anti cancer agents. For this reason, we have evaluated p53 alterations in 282 consecutive patients with infiltrating node-negative breast cancer who underwent primary surgery and were randomized either to CMF (Cyclophosphamide 400 mg/m2, Fluorouracil 400 mg/m2, and Methotrexate 40 mg/m2) or control arm (no adjuvant therapy) from 1980 to 1989. p53 alterations were analyzed by immunohistochemistry using DO7 MoAb, revealed by immunoperoxidase technique, and quantitated in term of percentage of positive cells. We observed a positive staining in 24% of the tumors. Among them, 10% had a positive staining in more than 75% of the cells. There was a highly significant association between the proportion of positive cells and histologic grade of the infiltrating ductal carcinomas (p<0.004). However, there was no association with age, tumor size, hormone receptor content, or vascular embolism. There was a trend but no significant relationship between positive staining and overall survival either in each arm of the trial or in the overall population. Interestingly, we observed a higher relative risk of local relapse after conservative therapy in the boosted area in the group of mutated p53 (RR=4.41; p<0.0005). We conclude that, in this node-negative breast tumor population, alteration of p53 cannot predict the response to the chemotherapy. However, it may represent a useful marker of risk of local relapse and of radio resistance.
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PMID:Is p53 a protein that predicts the response to chemotherapy in node negative breast cancer? 949 75

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

We studied c-erbB-2, p53, and nm23 gene products in 112 primary breast carcinomas. Fifty patients were aged 35 years or younger, and 62 were aged 36 to 50. Clinicopathological criteria including clinical stage, hormone receptor status, histological types, histological grades, and lymph node status, were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed. Immunohistochemical findings were assessed semiquantitatively. Correlation between clinicopathological criteria, survival data, and immunohistochemical findings have been made. Patients aged younger than 35 years with stage I to II disease had a shorter DFS (P = .03) than older patients. However, no other clinicopathological finding was associated with age. Neither was there association between age and c-erbB-2, p53, or nm23 patterns of expression. p53 positivity was associated with high histological grade (P = .003) and with progesterone receptor negativity (P = .045). Nm23 nuclear positivity was associated with early clinical stages (P = .011) and with absence of axillary lymph node metastasis (P = .007). p53 and c-erbB-2 overexpression were associated with shorter OS while nm23 nuclear positivity was associated with longer OS in univariate and multivariate analyses. Univariate analyses showed that c-erbB-2 or nm23 were potentially important prognostic factors in women aged 35 years or younger while p53 was associated with prognosis in women aged 36 to 50. Cox model analysis indicated that c-erbB-2 alone was associated with prognosis in women 35 years and younger, whereas p53 alone was associated with prognosis in 36- to 50-year-old women. These results suggest that breast cancer in the youngest women has some biological specificity.
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PMID:C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: immunohistochemical analysis and clinicopathologic correlation. 956 80


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