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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel quantitative luminometric immunoassay (LIA) has been developed for the measurement of wild-type and mutant p53 protein in extracts from breast tumour tissue. The LIA was found to yield reliable estimates of p53 expression in cytosol samples routinely prepared for steroid receptor analysis as compared with results obtained with immunohistochemical analysis. The LIA was evaluated on 205 primary breast tumour cytosols prepared for steroid receptor analysis and stored frozen at -80 degrees C for 6-8 years, p53 protein being detected in 65% of the samples (range 0.01-23 ng mg-1 protein). Using an arbitrary cut-off value of 0.15 ng mg-1 protein, 30% of the tumours were classified as manifesting p53 overexpression. Significant and independent correlations were found to exist between p53 overexpression and shorter disease-free (P < 0.001) and overall survival (P = 0.039) at a median duration of follow-up of 50 months. p53 overexpression was related to low oestrogen receptor content and high proliferation rate (S-phase fraction). No relationship was found to tumour size or the presence of lymph node metastasis. Three tumours possessed an extremely high p53 content (> 10 ng mg-1 protein), all of which were of medullary or high-grade ductal type, oestrogen and progesterone receptor negative, DNA non-diploid, had S-phase fractions of > 22% and recurred within 1-2 years. In summary, a new sensitive and quantitative LIA suitable for routine analysis of p53 protein in steroid receptor cytosol preparations from breast tumours has been developed to confirm the prognostic importance of p53 protein accumulation in human breast cancer.
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PMID:Prognostic significance of p53 overexpression in primary breast cancer; a novel luminometric immunoassay applicable on steroid receptor cytosols. 773 92

The pathological and biological features of a consecutive series of impalpable invasive breast carcinoma, detected by mammography in the prevalent round of the breast screening programme, have been compared with a clinically presenting group of carcinomas in age-matched patients. There was a significantly higher prevalence of tubular carcinomas as well-differentiated infiltrating ductal carcinomas in the mammographically detected group, and a lower prevalence of poorly differentiated infiltrating ductal carcinomas. Lymph node metastasis was found in 6.5% of the impalpable group compared with 53% of the clinical group. The prevalence of oestrogen receptor was much higher in the impalpable group (96%) than in the control group (67%), although there were no significant differences for progesterone receptor. The prevalence of pS2 was also much higher in the impalpable group, as was cathepsin D. This finding is surprising in view of the reported relationship between cathepsin D and poorer survival. p53 and c-erb-2 proteins were detectable in fewer impalpable carcinomas. The mean MIBI (Ki-67) index was lower in the impalpable group (11.6) than in the clinical group (15.25). Within the mammographically detected group there was a significant difference in the MIBI index between tubular carcinomas and the different grades of infiltrating ductal carcinomas, with a wide range in each category but no association with size. The impalpable carcinomas detected by mammography differ from clinically presenting carcinomas in many ways, raising the question of whether a proportion or all would progress (dedifferentiate) with time.
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PMID:Pathological and biological features of mammographically detected invasive breast carcinomas. 759 62

Experimental studies have shown that the 67-kDa laminin receptor (LRec) is an important molecule for the interaction of tumour cells with the extracellular matrix, and that it plays a role in the early steps of angiogenesis and in tumour invasion and metastasis. We performed a multi-parametric study in 171 node-negative breast cancers, followed for a median time of 6 years, to verify whether determination of the LRec provides prognostic information in addition to intra-tumoral microvessel density (IMD), a measure of tumour angiogenesis, and to other biological and conventional indicators. A positive association between LRec expression and high neovascularization was found, although it did not reach significance. LRec was not associated either with other biological markers (oestrogen receptor, progesterone receptor and p53 expression) or to the conventional prognostic features [menopausal status, tumour size, histological types, grading and peri-tumoral lymphatic vessel invasion (PLVI)]. In univariate analysis, IMD, p53, PgR, PLVI, grading and tumour size were significant prognostic indicators of relapse-free survival (RFS). LRec expression approached significance when considered as a dichotomous variable, after having selected the optimum cutoff of 10% to distinguish high-risk from low-risk patients. For overall survival (OS), tumour size and IMD (continuous variable) were significant prognostic factors, and p53 approached significance. In multivariate analysis for RFS, the joint variable LRec and vascularization was the strongest independent prognostic factor, followed by PgR, PLVI and p53. For OS, tumour size was the only independent prognostic indicator in this series.
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PMID:67-kDa laminin-receptor expression adds prognostic information to intra-tumoral microvessel density in node-negative breast cancer. 786 Jan 33

This study investigates the mdm2 gene status and expression in 66 surgically resected human breast carcinomas, with correlations with clinico-pathological and biological data (histological type, grading, steroid receptor status, p53 expression, proliferative activity). Four (7.7 per cent) out of 52 informative cases bear mdm2 gene amplification (four-to ten-fold) and 8 (15.4 per cent) of 52 cases showed borderline amplification (three-fold). Nine (13.6 per cent) out of 66 cases showed strong mdm2 nuclear immunoreactivity. Twenty-seven (40.9 per cent) cases showed isolated mdm2 reactive nuclei. All cases with clear amplification showed a high percentage of mdm2 immunoreactive nuclei. The relationship between gene amplification and mdm2 protein expression is highly significant (P < 0.0001). No association was observed between mdm2 gene amplification and any of the considered clinico-pathological and biological parameters, while mdm2 immunoreactivity showed a significant association only with oestrogen receptor immunoreactivity (P = 0.009). p53 expression was associated neither with mdm2 gene amplification nor with mdm2 immunoreactivity. It could be tempting to hypothesize that the evaluation of the combined mdm2/p53 immunohistochemical phenotype in human breast carcinoma could give us better prognostic information than the evaluation of the expression of the p53 protein alone.
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PMID:mdm2 gene alterations and mdm2 protein expression in breast carcinomas. 789 Dec 24

The p53 gene product is a tumour suppressor protein, and alterations of the protein are common in human cancer. Previous studies have focused on nuclear accumulation of p53. To investigate if cytoplasmic accumulation of p53 strengthens the relationships to different pathobiological variables and distant recurrence-free survival in breast cancer, tumours from 164 stage II patients were examined with the monoclonal antibody PAb1801. Nine per cent of the tumours were nuclear positive and 21% were cytoplasmic positive. Cellular p53 accumulation, related to the nucleus or the cytoplasm or both, showed stronger associations with pathobiological variables than nuclear accumulation alone. Accumulation of p53 was significantly correlated to tumour size over 20 mm, negative oestrogen receptor (ER) status, DNA aneuploidy, high S-phase fraction and positive erbB-2 status. Cytoplasmic p53 was significantly correlated to distance recurrence-free survival in patients negative for nuclear p53 (P < 0.0001). Cellular p53 accumulation was an independent prognostic factor, in addition to lymph node status and ER content. We conclude that consideration of cytoplasmic staining enhances the clinical importance of p53.
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PMID:Cellular accumulation of p53 protein: an independent prognostic factor in stage II breast cancer. 790 19

The nm23 gene was originally identified by Steeg et al. by screening of cDNA libraries from murine melanoma cell lines of varying metastatic potential. An inverse relationship between metastatic potential and nm23 RNA and/or protein was found in four different metastatic model systems. It was proposed that nm23 may function as a suppressor gene for tumour metastasis. It has recently been found that the sequence of nm23 and NDP-kinase (NDP-K) is identical. Using an immunohistochemical technique and employing a polyclonal antibody to purified NDP-K A, we have determined NDP-K expression in a series of 197 breast carcinomas. One hundred and sixty (81.2 per cent) of these tumours were scored positive for NDP-K and 37 (18.8 per cent) scored negative. No relationship was found between NDP-K/nm23 expression and patient relapse or survival. Furthermore, no relationship was found between NDP-K/nm23 expression and a number of other prognostic factors including tumour grade, oestrogen receptor, progesterone receptor, and p53 expression. Our results contradict the hypothesis concerning the possible role of NDP-K/nm23 as a metastatic suppressor gene in human breast cancer, but further studies using antibodies specific for NDP-K/nm23 subtypes are clearly indicated.
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PMID:NDP-K/nm23 expression in human breast cancer in relation to relapse, survival, and other prognostic factors: an immunohistochemical study. 793 24

The MDM2 gene is a gene whose product binds to p53 and regulates its functions. The amplification of the MDM2 gene has been found in one third of human sarcomas, and a differential expression of MDM2 gene in relation with oestrogen receptor status was recently found in human breast cancer cell lines. We analysed 60 breast cancers for MDM2 gene amplification by Southern blot. This event was observed in 1 case with high levels of oestrogen receptor (ER). Thus, MDM2 gene amplification seems to be a rare event in breast cancer. Further studies are needed to define precisely the relationship between MDM2 amplification and ER status.
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PMID:MDM2 gene amplification in human breast cancer. 794 96

Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival.
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PMID:Prognostic significance of TP53 alterations in breast carcinoma. 810 35

The expression of three epidermal growth factor (EGF)-related peptides, transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 primary infiltrating ductal (IDCs) and infiltrating lobular breast carcinomas (ILCs), and in 23 adjacent non-involved human mammary tissue samples. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreactive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cytoplasmic staining was observed with all of the antibodies, and this staining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the antibodies was confined to the carcinoma cells, since no specific immunoreactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also exhibited nuclear staining in a number of the carcinoma specimens. No significant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen receptor status, axillary lymph node involvement, histological grade, tumour size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse correlation was observed between the average percentage of carcinoma cells that expressed AR in individual tumours and the presence of a point-mutated p53 gene. Likewise, a significantly higher percentage of tumour cells in the ILC group expressed AR as compared with the average percentage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected by ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonstrate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer.
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PMID:Expression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas. 818 21

The role of bcl-2 expression in solid tumours is as yet undefined. It was, therefore, the purpose of this study to investigate expression of bcl-2 protein in 111 human breast carcinomas using immunohistochemistry and the monoclonal antibody bcl-2 124. Expression was then compared with the established indicators of prognosis and biological behaviour in malignant breast disease. No relationship could be observed between bcl-2 and node status, tumour size, differentiation, type or age at excision. However, a strong positive relationship was seen between bcl-2 and oestrogen receptor (ER), with 70 of 88 (80%) bcl-2-positive tumours being ER positive also, compared with seven of 23 (30%) bcl-2-negative tumours being ER positive (P < 0.0001). The converse was found when bcl-2 was compared with epidermal growth factor receptor (EGFR). A strong negative relationship was observed, with 26 of 88 (30%) bcl-2-positive tumours being EGFR positive, compared with 16 of 23 (70%) bcl-2-negative tumours being EGFR positive (P = 0.001), raising the possibility that bcl-2 is an ER-regulated gene. An inverse relationship was also found between bcl-2 and the oncogenes c-erbB-2 and p53. Thus, loss of bcl-2 expression in breast cancer is associated with a range of molecular markers of poor prognosis and may define part of an ER-negative, EGFR-positive phenotype.
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PMID:bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. 828 95


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