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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TP53 is a gene that normally regulates cell growth and division. Alterations to it may induce a proliferative advantage and confer an aggressive phenotype. In breast cancer, we observed a poor correlation (rs = 0.17) between P53 expression and proliferative activity evaluated as [3H]-thymidine ([3H]-dT) labeling index and an independent prognostic relevance of the two variables. We used a double-labeling technique to simultaneously evaluate the fraction of P53-positive and [3H]-dT-labeled cells to analyze the degree of association between the two markers on individual cells in order to understand their biological significance. The study was performed on a series of 44 P53-positive (P53+) breast cancers. Histological sections were immunostained for P53 with monoclonal antibody (MAb) PAb1801 and then processed for autoradiography. A weak direct relation between P53 positivity and [3H]-dT incorporation (rs = 0.4) was observed on the overall series of P53+ tumors and was maintained in subgroups defined by several biological and pathological features, except for estrogen receptor-negative tumors. The simultaneous presence of P53 expression and [3H]-dT incorporation was directly and significantly proportional to the fraction of S-phase cells of the tumor (rs = 0.7). Conversely, the fraction of cells expressing only P53 was inversely related to cell proliferation (rs = -0.66). These findings support the hypothesis that P53 has biological functions other than cell cycle regulation.
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PMID:Detection of P53 expression and S-phase cell fraction in paraffin-embedded tissue by a double-labeling technique. 756 Aug 90

In a retrospective study, 204 formalin-fixed and paraffin-embedded biopsies of primary breast carcinomas were tested immunohistochemically for the expression of p53 protein (PAb 1801). 38% of the carcinomas were positive with respect to p53. The expression of p53 correlated significantly with the loss of tumor differentiation (P = 0.013), but not with menopausal status, patients' age, tumor size, axillary lymph node involvement or hormone receptor status. The influence of p53 expression on prognosis was evaluated in 197 patients (T1-4 N0-2 M0, median observation time 72 months). Detection of p53 protein was associated with a significantly longer disease-free survival in node-positive women (P = 0.03). However, p53 protein did not prove to be a prognostic factor in node-negative patients. The results demonstrate the prognostic value of p53 expression in breast cancer which appears to be limited to patients with node-positive tumors.
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PMID:P53 protein in 204 patients with primary breast carcinoma--immunohistochemical detection and clinical value as a prognostic factor. 757 6

Functional p53 protein is essential for the cellular response to drug-induced DNA damage. We investigated p53 accumulation in tumour specimens from premenopausal breast cancer patients who were randomised to adjuvant chemotherapy (CMF) or postoperative radiotherapy. Of the tumours from 139 patients, 20 showed abnormal accumulation as judged with immunohistochemistry (> 10% positive tumour cells). The risk of distant recurrence was similar in the two treatment groups for patients whose primary tumours lacked p53 accumulation, whereas there was a significant benefit from CMF for patients showing abnormal accumulation (relative risk 0.18, 95% CI, 0.04-0.93). This result suggests that p53-dependent apoptosis is not a general mechanism by which breast cancer cells respond during CMF chemotherapy.
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PMID:p53 expression and the result of adjuvant therapy of breast cancer. 757 43

Exposure of human cells to gamma-radiation causes levels of the tumour-suppressor nuclear protein p53 to increase in temporal association with the decrease in replicative DNA synthesis. Cells from patients with the radiosensitive and cancer-prone disease ataxia telangiectasia (AT) exhibit radioresistant DNA synthesis and show a reduced or delayed gamma-radiation-induced increase in p53 protein levels. We have used Western immunoblotting with semiquantitative densitometry to examine the gamma-radiation-induced levels of p53 protein in 57 lymphoblastoid cell lines (LCLs) derived from patients with AT, carriers of the AT gene, breast cancer patients and normal donors. We confirm the previously reported reduced induction in AT homozygote LCLs (n = 8) compared with normal donor LCLs (n = 17, P = 0.01). We report that AT heterozygote LCLs (n = 5) also have a significantly reduced p53 induction when compared with LCLs from normal donors (n = 17, P = 0.02). The response of breast cancer patient cells was not significantly different from normal donor cells but 18% (5/27) had a p53 response in the AT heterozygote range (95% confidence interval) compared with only 6% (1/17) of the normal donor cells. We found no significant correlation between p53 induction and cellular radiosensitivity in LCLs from breast cancer patients. These methods may be useful in identifying individuals at greater risk of the DNA-damaging effects of ionising radiation.
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PMID:Induction of p53 protein by gamma radiation in lymphocyte lines from breast cancer and ataxia telangiectasia patients. 757 53

We established a panel of 17 xenografts from primary human breast carcinomas. We examined which characteristics of the original tumours and the xenografts facilitate growth in animals. Tumours expressing medium or strong immunoreactivity for p53 protein had significantly (P < 0.05) higher incidence (92%) of in vivo tumour take than those showing weak or negative immunoreactivity (9.1%). No such association was observed between either c-erbB-2 or epidermal growth factor receptor (EGFR) expression in the original tumours and their in vivo tumour take. Following subcutaneous (s.c.) transplantation of original breast tumours or established xenografts, 7/17 tumours showed metastatic disease spread to distant sites (mainly lungs). This study suggests that selective growth of highly aggressive tumours occurs during in vivo propagation of malignant tumours, and these tumours will be of particular interest in evaluating various chemotherapeutic agents for breast cancer management.
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PMID:Overexpression of mutant p53 and c-erbB-2 proteins and breast tumour take in mice. 757 62

Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.
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PMID:Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy. 757 79

P53 immunohistochemical detection using DO7 antibody on 942 cases of previously untreated breast invasive ductal carcinoma (IDC) with a median follow up of 117.9 months (89 to 160) was performed. Three hundred and three (32%) tumors were positive. All positive tumors were taken into account, positivity ranging from 1 to 100% of tumoral cells. The Chi square test showed significant negative correlation between p53 positivity and age (p = 0.01), estrogen receptor status (p < 0.0001), and progesterone receptor status (p = 0.0005), and significant positive correlation with tumor grade according to the Scarff, Bloom and Richardson system (SBR Grade) (p < 0.0001). There was no significant association with tumor size or nodal status. Concerning the univariate analysis, in the whole group and node-positive group (n = 544) p53 positivity was highly significant for overall survival (OS) (p < 0.0001 and p = 0.0003), disease-free interval (DFI) (p = 0.0001 and p = 0.0005), and metastasis-free interval (MFI) (p < 0.0001 and p = 0.0003). In the node-negative group (n = 398), p53 was significant with respect to OS (p = 0.01) and DFI (p = 0.04). P53 positivity came out as an independent prognostic parameter in the multivariate analysis in the whole group and the node-positive group, though of minor significance compared to axillary lymph node status, SBR grade, progesterone receptor status and tumor size.
Breast Cancer Res Treat 1995
PMID:Prognostic value of p53 in breast invasive ductal carcinoma: an immunohistochemical study on 942 cases. 757 9

The mutation of the p53 gene is a common phenomenon in numerous human tumors, leading to the accumulation of nonfunctioning p53 protein in the cell nucleus, which can be detected by immunohistochemistry. In breast cancer, it has been suggested that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, which must be borne in mind in selecting coadjuvant treatment for each patient. This study is an immunohistochemical analysis of p53 expression in 153 cases of mammary carcinoma, correlating it with histological grade, axillary node status, hormone receptors, cell-proliferation fraction and expression of the c-erbB-2 oncoprotein. Of all the breast-cancer tissue analyzed, 43.79% was positive for p53. The overexpression of this protein bears a direct statistically significant relationship to histological grade, cell-proliferation fraction and c-erbB-2, and an inverse relationship to estrogen and progesterone receptors. No statistically significant relationship was found with axillary node status. The expression of p53 in poorly differentiated tumors-commonly receptor negative and with a high proliferation fraction-may indicate greater tumor aggressiveness and a high risk of relapse.
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PMID:p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistochemical study of 153 cases. 757 1

We evaluated the prognostic value of tumor angiogenesis in node negative breast cancer (NNBC). Paraffin-embedded tissues from 87 patients with NNBC were immunostained for factor VIII-related antigen, using one tissue block representative of the invasive edge of the tumor. Sections were scanned at low power to identify "hotspots" of angiogenesis. Microvessel (MV) counts were performed at x200 magnification, using a grid eyepiece graticule. Within each hot spot, three fields (area of field = 0.22 mm2) were counted and averaged. The highest average for a hot spot and the highest single field value was recorded for each case. Patients were stratified into low and high MV groups and their survival compared. There were no differences in disease-free or overall survival between the two groups whether the highest average or the highest single value was used. Microvessel counts did not correlate with other prognostic features, ie, grade, size, estrogen receptor status, c-erb B-2 or accumulated P53 status. Because of the difficulty in assessing angiogenesis that is heterogenous throughout tumors, MV counting may not be suitable for clinical use as a prognostic factor in NNBC. This problem could be addressed in a prospective study involving more extensive tumor sampling.
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PMID:Prognostic significance of microvessel density in lymph node negative breast carcinoma. 759 Jun 87

Studies on the molecular basis of human breast cancer have demonstrated that mutational inactivation of the p53 tumor suppressor gene may be an essential step in the development of this cancer. We and others have previously shown that transfer of the wild-type p53 gene into cultured breast cancer cells reduced their malignant potential. We report here on a p53 gene transfer protocol based on a replication-incompetent retrovirus to efficiently inhibit tumor formation of cancer cells with endogenous mutant p53. The susceptibility of the cells to retroviral infection was determined with LZRNL transducing the lacZ reporter gene. A multiplicity of infection (moi) of 2 resulted in 90% of the exposed cell population in cytochemically detectable beta-galactosidase activity. Using the p53 vector Lhp53RNL with a moi of 2 was sufficient to completely supress tumor formation by the highly tumorigenic MDAMB231 breast cancer cells carrying a point missense mutation in codon 280. Even after 12 weeks, no vital tumors were histologically detectable. For comparison, established protocols were used to infect MDAMB231 cells with low moi with the p53 virus. Clones were expanded in G418-selective media for few weeks, pooled and injected into nude mice. Tumor formation occurred already after 1 week from G418-selected cells. Long-term expression of the p53 transgene was more stable in retrovirally bulk-infected and nonselected cells resulting in an efficient suppression of tumor formation. This approach may facilitate future studies on other growth suppressive genes that potentially qualify for in vivo gene therapy.
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PMID:p53 trans-dominantly suppresses tumor formation of human breast cancer cells mediated by retroviral bulk infection without marker gene selection: an expeditious in vitro protocol with implications towards gene therapy. 759 Jul 73


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