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)

Vimentin, p53 protein and cathepsin D positivity were assessed by immunohistochemistry, and oestrogen receptor (ER) by an enzyme immunoassay, in invasive lobular carcinomas (LC) of the breast. While vimentin was positive in only 5% (3/57) and p53 protein was positive only in 3% (2/63), cathepsin D was expressed in 86% (48/56) and ER in 78% (25/32). Classical LC were negative for p53 protein and all except one were cathepsin D positive. These results are in contrast to invasive ductal breast carcinomas (DC), where the reported average incidence of vimentin and p53 protein is much higher (19% and 33% respectively) and that of cathepsin D and ER lower (63% and 67% respectively). Thus lack of expression of vimentin and lack of p53 positivity together with high incidence of expression of cathepsin D and ER are more often associated with lobular than with ductal differentiation of invasive breast cancer. The results show that LC, distinguished morphologically, can further be defined by its immunohistochemical profile. This in turn may point to underlying biological differences between LC and DC.
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PMID:Immunohistochemical profile of invasive lobular carcinoma of the breast: predominantly vimentin and p53 protein negative, cathepsin D and oestrogen receptor positive. 829 Dec 22

In 216 breast cancer patients, the prognostic value of current biological factors (c-erbB-2, EGF-receptor, p53, PCNA-proliferative fraction) was compared with that of conventionally histomorphologic features (histologic type, histologic grade, tumour size, hormonal receptor status). After a 66(6 - 109) months' median follow-up survival was significantly correlated with histological grade (p = 0.014) and PCNA-proliferative activity (p = 0.015). The prognostic influence of oestrogen receptor (ER)- and progesteron receptor (PR-)status achieved borderline significance (ER/p = 0.07; PR/p = 0.05). Neither c-erbB-2, EGF-R, p53 nor any of the other factors showed any correlation to survival. In the multivariate analysis, histological grade was revealed as the only independent prognostic factor. The prognostic value of PCNA was second to histological grade and if grade was excluded from the analysis, PCNA-expression became the only independent factor. Thus, in individual cases the PCNA-proliferative fraction could help the clinician to decide on the therapy.
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PMID:[C-erbB-2, EGF receptor, p53 and PCNA. The prognostic significance of recent tumor markers for lymph node negative breast cancer]. 854 29

We examined the reactivity of four p53-specific monoclonal antibodies--PAb 1801, p53-BP-12, D07 and CM1--on sections of formalin-fixed tissue collected from 245 breast carcinomas. Immunodetection of p53 varied between 37.6% and 46.6%. The greatest variation was observed among lobular carcinomas and low-grade tumors in which immunodetection varied between 8.3% and 27.3%. In contrast, immunodetection of p53 in invasive ductal carcinomas was subject to a lower degree of variability with between 40.6% and 49.7% of these tumours proving to be positive. In general, we found antibodies PAb 1801 and DO7 to be the most effective in immunolocalising p53. Immunodetection of p53 with each of the four antibodies was found to correlate strongly with tumour grade. In survival analysis, the results gained using antibody PAb 1801 proved to be of greatest statistical significance and to provide the strongest index of prognosis. A significant relationship was observed between immunodetection of p53 with each of the four antibodies and poor responsiveness to endocrine therapy. In addition, relationships were also observed between p53 immunostaining and tumour oestrogen receptor (ER) status as well as c-jun expression. We observed no correlation between abnormalities of the p53 and the Rb gene products or between elevated c-erbB-2 or epidermal growth factor receptor (EGFR) expression and immunodetection of p53.
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PMID:p53 protein as a prognostic indicator in breast carcinoma: a comparison of four antibodies for immunohistochemistry. 855 79

Overexpression of cyclin D1 is frequently found in various types of human tumours and results from clonal rearrangement and/or amplification involving chromosomal region 11q13. In order to evaluate the pathological relevance of cyclin D1 overexpression in human breast cancer, we generated a polyclonal antiserum against the carboxy-terminal part of the cyclin D1 protein. After affinity purification, the antiserum specifically detected overexpression of cyclin D1 in formalin-fixed, paraffin-embedded tumour material also. The intensity of the nuclear stainings was, in general, proportional to the degree of cyclin D1 amplification. We did not encounter significant variability of staining within individual tumours with overexpression of cyclin D1. Overexpression of cyclin D1 appeared to be associated with oestrogen receptor-positive breast tumours, but not with any other clinicopathological parameter tested. Overexpression of cyclin D1 was not prognostic value for recurrence of survival in a consecutive series of 248 operable breast cancer patients (stage I and II). Overexpression of p53 was also not of prognostic significance in this series, but was associated with undifferentiated histology and oestrogen receptor-negative breast tumours, as has been reported previously by others. A high proportion of breast tumours with a low grade of malignancy in this series of operable breast cancer patients may explain discrepancies concerning the prognostic value of amplification and of overexpression of cyclin D1.
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PMID:A clinicopathological study on overexpression of cyclin D1 and of p53 in a series of 248 patients with operable breast cancer. 861 72

Breast cancer prognosis has previously been linked to the degree of tumour vascularisation. In order to establish additional markers for tumour angiogenesis, we have used monoclonal antibodies against the endothelial Tie receptor tyrosine kinase to study the degree of vascularisation of breast carcinomas and the regulation of Tie expression in the vascular endothelial cells. Antibodies were used for Tie detection and the results were correlated with other prognostic markers. Of four monoclonal antibodies directed against different epitopes of the Tie extracellular domain, two reacted against Tie in unfixed histopathological sections of breast carcinomas. One of these antibodies (clone 7e8) was specific for the endothelial cells whereas the other (clone 10f11) also reacted with basement membranes and occasional carcinoma cells. When Tie expression was studied with the antibody clone 7e8, all 27 carcinomas, two in situ carcinomas, samples of histologically normal breast tissue (n = 16) or normal skin or lymph node tissue (n = 5) showed staining. Microvessel counts were higher in carcinomas (median 14; range 3-27) than in fibrodenomas (median 10; range 5-18) or histologically normal breast tissue (median 7; range 3-15, P = 0.0006). A similar result was obtained using antibodies against the CD31 (PECAM) antigen. Microvessel counts in 7e8 staining were not significantly associated with primary tumour size, axillary nodal status, histological grade or staining for oestrogen receptor, progesterone receptor, Ki-67 proliferation marker or p53 oncoprotein.
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PMID:Endothelial Tie growth factor receptor provides antigenic marker for assessment of breast cancer angiogenesis. 867 61

Serum p53 autoantibodies were studied in 82 patients with Stage 1 or 2 breast cancer using an ELISA assay. Tissue expression of p53 in these patients was also examined. High levels of serum p53 autoantibodies were detected in 48% (39/82) patients, while 23% (19/82) were tissue positive. Patients with high serum p53 autoantibodies levels were not significantly different to those with low levels with respect to, tissue p53, tumour grade, size, stage or oestrogen receptor status. Tissue immunoreactivity for p53 was significantly associated with tumour grade and negative oestrogen receptor status. Patients in both groups were followed for a median of over five years but the presence of p53 autoantibodies in serum was not prognostic with respect to disease free interval or survival. In this study detection of p53 autoantibodies in serum does not correlate with any of the usual tumour related prognostic factors, nor does it correlate with clinical outcome.
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PMID:The significance of p53 autoantibodies in the serum of patients with breast cancer. 868 53

p21 protein (p21) inhibitor of cyclin-dependent kinases is a critical downstream effector in the p53-specific pathway of growth control. p21 can also be induced by p53-independent pathways in relation to terminal differentiation. We investigated p21 immunoreactivity in normal breast and in 91 breast carcinomas [three in situ ductal carcinomas (DCIS) with microinfiltration and 88 infiltrating carcinomas, 17 of which with an associated DCIS; 57 node negative and 34 node positive] with long-term follow-up (median = 58 months). Seven additional breast carcinomas with known p53 gene mutations were investigated. In normal breast p21 expression was seen in the nuclei of rare luminal cells of acinar structures, and in occasional myoepithelial cells. Poorly differentiated DCIS showed high p21 expression, whereas well-differentiated DCIS tumours showed few p21-reactive cells. p21 was seen in 82 (90%) infiltrating tumours; staining was heterogeneous; the percentage of reactive nuclei ranged from 1% to 35%. High p21 expression (more than 10% of reactive cells) was seen in 24 (26%) cases, and was associated with high tumour grade (P = 0.032); no associations were seen with tumour size, metastases, oestrogen receptor status, MIB1 expression and p53 expression. p21 expression in cases with p53 gene mutations was low in six cases and high in one. High p21 expression was associated with short relapse-free survival (P = 0.003).
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PMID:p21WAF1 immunohistochemical expression in breast carcinoma: correlations with clinicopathological data, oestrogen receptor status, MIB1 expression, p53 gene and protein alterations and relapse-free survival. 868 23

The immunohistochemical expression of p53 and c-erbB-2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c-erbB-2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow-up time: 6 years). The expression of p53 protein and c-erbB-2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c-erbB-2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c-erbB-2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno-expression was clearly associated with c-erbB-2 protein overexpression. Concomitant p53 and c-erbB-2 positive immunolabelling, which emerged in 14 out of the 130 cases (10.7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c-erbB-2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c-erbB-2 positive phenotype. The simultaneous immunodetection of p53/c-erbB-2 appears to have greater negative prognostic relevance than their separate expression.
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PMID:Prognostic significance of the co-expression of p53 and c-erbB-2 proteins in breast cancer. 869 41

The aim of this investigation was to examine the possibility of analysing TP53 mutations in archival paraffin-embedded material with the constant denaturant gel electrophoresis (CDGE) method. We extracted DNA from 193 archival primary breast carcinoma samples, diagnosed in 1981-83; further analysis was possible for 186 of these. TP53 mutations in exons 5-8 were detected with CDGE in 30 samples (16.1%) and 17 of these mutations were confirmed by sequencing. Immunohistochemistry demonstrated TP53 nuclear accumulation in 58 tumours (31%). A strong association between the presence of TP53 mutations and TP53 immunostaining was observed (P < 0.001). Our mutation and immunohistochemistry results are in agreement with other findings based on fresh tumour tissue. TP53 abnormalities were significantly related to high S-phase fraction, low oestrogen receptor (ER) content and high tumour grade. Survival of patients with TP53 abnormalities, in the group as a whole, did not differ from patients with normal TP53. Our study did, however, show that patients with abnormal TP53 had a significantly shorter post-recurrence survival (P = 0.005) than patients with normal TP53.
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PMID:TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded archival material. 876 69

We have assessed the multiple biological variables on breast carcinoma FNA specimens using a Cytoblock technique. The growth fraction (MIB1), oestrogen receptor (ER), progesterone receptor (PR), p53 mutant protein, c-erbB-2, epidermal growth factor receptor (EGFR), NCRC11/epithelial membrane antigen (EMA) and DNA plopidy were examined. Objective quantification using image analysis (CAS 200) was applied as appropriate. Fifty cases were examined in this preliminary study. Excellent correlation between the Cytoblock preparations and parallel tissue sections was seen. Of the cancers, 81% were aneuploid with only 19% diploid in character, but 67% of the carcinomas were of histological grade 3. The mean nuclear area staining with MIB1 was 31.3% and with ER was 26.7%. Twenty-four percent (24.1%) of the nuclear area showed immunoreactivity with PR. Significant EGFR and EMA, respectively. A significant association between histological grade of the resected tumours and both MIB1 (P = 0.04) and EGFR (P = 0.02) expression in the Cytoblock samples was seen. p53 (P = 0.03) and EGFR (P = 0.01) immunoreactivity showed an association with tumour size. EGFR (P = 0.04) immunostaining also showed a relationship with the lymph node status of the patient. The technique is, we believe, a useful one for the assessment of multiple variables on breast cytology specimens; these preliminary data suggest that some of these may be useful in predicting prognosis in breast cancer patients.
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PMID:The assessment of multiple variables on breast carcinoma fine needle aspiration (FNA) cytology specimens: method, preliminary results and prognostic associations. 878 69


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