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)

Biopsy specimens from 177 bladder tumours were analysed by immunohistochemical methods for the expression of cathepsin D. Strong expression of cathepsin D was detected in transitional carcinoma cells in 40 per cent of cases. Umbrella cells were positive in 29 per cent of cases and a cathepsin D-positive cell zone composed of tissue macrophages was detected at the invasion front in 34 per cent of tumours. Strong expression of cathepsin D was related to muscle invasive growth phase (T > or = 2) (P = 0.019), grade 2-3 histology (P = 0.008), S-phase fraction over 10 per cent (P = 0.032), and overexpression of epidermal growth factor receptor (EGFR) (P < 0.001). Umbrella cells were positive in low-grade (P = 0.03) papillary tumours (P = 0.02) with an S-phase fraction < or = 10 per cent (P = 0.02). Cathepsin D was expressed in macrophage-like cells in the invasion front in tumours which were densely infiltrated by inflammatory cells (P = 0.017) and in tumours overexpressing EGFR (P = 0.017) or p53 protein (P = 0.007). Progression in N- (P = 0.04) and M-categories (P = 0.01) was related to strong expression of cathepsin D in cancer cells and in univariate survival analysis; this was weakly related to poor outcome (P = 0.09). In multivariate analysis, papillary status (P = 0.055) and S-phase fraction (P = 0.079) predicted prognosis in Ta-1 tumours. In T2-4 tumours, T-category (P < 0.001), papillary status (P < 0.001), S-phase fraction (P = 0.028), and the presence of cathepsin D-positive tissue macrophages (P = 0.017) were independent prognostic factors.
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PMID:Expression of cathepsin D in transitional cell bladder tumours. 877 18

A series of 30 cases of male breast cancer in the North-East of Scotland is reviewed. The aims of the study were to document clinico-pathological and immunocytochemical features (available for 25) of these patients and to establish which factors could predict prognosis. Tumours were studied for the expression of oestrogen receptors (ERs), the oestrogen-dependent proteins pS2 and cathepsin D, the oncoprotein products of c-erb-B2 and the p53 tumour-suppressor-gene derived protein. Clinico-pathological features documented were in agreement with those reported by other authors. The overall 5-year survival was 53%. Tumour grade and lymph-node status influenced prognosis. In this series, 64% of the tumours expressed ERs, 50% pS2, 46% cathepsin D, 42% the c-erb-B2 transmembrane oncoprotein and 54% p53. In contrast to female breast cancer, the presence of either substantial amounts of ERs or the oestrogen-dependent protein pS2 correlated with poorer prognosis in males. This correlation has not previously been documented.
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PMID:Male breast cancer: clinico-pathological features, immunocytochemical characteristics and prognosis. 884 66

The immunohistochemical overexpression of p53 protein in 42 large bowel cancers was correlated to c-erbB-2, cathepsin D (CD) proteins and other clinical and prognostic parameters. p53 overexpression (found in 60% of specimens) was positively associated with cathepsin D staining in stromal cells from older patients and better differentiated colorectal carcinomas (G1 + G2). Cytoplasmatic staining of c-erbB-2 protein was found in 58% of cases. No staining was observed at the cell membrane level. Our findings suggest that lower p53 expression in G3 carcinomas may be due to a high genomic instability, with the loss of both alleles of the gene. Therefore, these carcinomas were immunohistochemically silent. Although our series was small, the association between p53 nuclear neoplastic cells and CD stromal cells is interesting as regards the possible implications of these markers in colorectal cancer.
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PMID:Immunohistochemical p53 overexpression correlated to c-erbB-2 and cathepsin D proteins in colorectal cancer. 904 63

CD44 variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines. CD44v6 overexpression correlates tumor dedifferentiation and progression in some human carcinomas, but the relationship of CD44v6 overexpression with metastatic behavior of tumor observed in animal models is controversial, particularly in breast carcinomas. The discrepancies probably result from analytical bias. We investigated CD44v6 and CD44s expression in 218 frozen samples of primary breast carcinomas. Immunocytochemical procedure was performed under optimal technical conditions using commercially available 2F-10 monoclonal antibody (MAb), a microprocessor-controlled automated device (Ventana Medical Systems, Tucson, AZ), and quantitative evaluation of results by processing digitized-colored microscopic images (SAMBA, Grenoble, France). CD44v6 expression in tissue sections was shown to be independent of the patient age, tumor size, histological types and grades, and the lymph node status. CD44v6 expression was also independent of the expression of molecules endowed with poor prognostic significance detected by MAbs (anti-p53, anti-c-erb B-2 protein, MIB1) on consecutive sections. No significant relationship could be evidenced either between CD44v6 expression, and CD31 involved stromal angiogenesis and cathepsin D. Finally, CD44v6 was independent of markers of hormone dependence (estrogen and progesterone receptors, pS2) and of multidrug resistance (P-glycoprotein). Similar results were observed with anti-CD44s. We conclude that the true prognostic significance of CD44v6 overexpression still remains to be shown under rigorous technical conditions (frozen samples, well-documented MAbs, and optimal standardization of procedure using automation and quantitative analysis) providing data appropriate for further correlation with long-term patient follow-up.
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PMID:Automated and quantitative immunocytochemical assays of CD44v6 in breast carcinomas. 904 92

Even among breast cancer patients without metastasis to axillary lymph nodes, early recurrence can occur. To determine the risk factors for early recurrence, we performed a case-control study between 32 patients with an early recurrence of breast cancer and 122 patients without recurrence, in which tumor size, age of patient and date of operation were matched. In all 154 node-negative patients, followed up over a 13.1-year median period, expression of p53, c-erbB-2 and cathepsin D in the primary tumor were studied immunohistochemically in paraffin-embedded tissues and were compared with morphologic factors such as histologic grade and invasive growth. Univariate analysis showed that nuclear p53 immunoreaction was significantly predictive of early recurrence [risk ratio (RR) 3.3]. Likewise, cathepsin D (RR 0.22) was significantly negatively associated; however, when the risk ratio was analyzed in terms of intensity of cathepsin D staining, no superior survival was found for patients with strongly positive tumors. Overexpression of c-erbB-2 protein was not associated with outcome by either univariate or multivariate analysis. As a whole, histologic grade was confirmed as being a strong predictor (RR 42.6) and multivariate analysis showed that only histologic grade was a significant risk factor for early recurrence. p53 immunoreaction was not a significant independent factor because it was closely linked to histologic grade (P = 0.002), especially to a high mitotic index (P < 0.001). Moreover, in 14 patients with "special histologic types' of invasive carcinomas and no recurrence, all were p53-negative except one medullary carcinoma. Nuclear p53 immunoreaction is useful in supporting histologic grade to detect a high-risk for early recurrence in node-negative patients who may be eligible for systemic adjuvant therapy.
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PMID:Histologic grade and p53 immunoreaction as indicators of early recurrence of node-negative breast cancer. 907 Mar 33

A long list of potential prognostic markers has been analysed for breast cancer, some of them will be reviewed in this article. The lymph node status is still the best prognostic marker. The lymph node status combined with information on tumour size, receptor- and proliferation status of the tumour should be analysed as standard for all breast cancer patients. Prognostic information for breast cancer patients has also been described for the membrane protein c-erbB2, the protease cathepsin D, plasminogen activators and inhibitors, certain oncogenes and tumour suppressor genes. Some of these factors also give potential additional information on the response to different oncological therapies, and are better denoted predictive factors. In this overview we shortly describe the above mentioned prognostic factors with major focus on the tumour suppressor gene p53 and its prognostic value and potential predictive value.
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PMID:Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53. 914 77

The reduction of E-cadherin expression, which is involved in the initial step of invasion and metastasis of cancer, was investigated in 218 human breast carcinomas. Quantitative immunohistochemical assays (ICAs) were performed on frozen sections. Quantitation was assessed by processing digitized microscopic images of immunoreactions using a computerized system of image analysis (SAMBA). The results were correlated with clinicopathological data and quantitative immunodetection of other molecules. E-cadherin expression was significantly (P < 0.001) stronger in ductal carcinomas than in lobular carcinomas and stronger (P < 0.01) in low grades than in high grades, but E-cadherin was independent of lymph node status and tumour size. Also an inverse significant (P < 0.01) relationship was observed between E-cadherin expression on tissue sections and positive immunoreactions with anti-P53, MIB1 (growth fraction), and anti-c-erb-B2 product. Conversely, strong positive and anti-E-cadherin immunoreactions correlated with strong positive anti-ER and anti-PR immunoreactions (P < 0.01). No relationship was observed between E-cadherin and the results of quantitative ICAs of cathepsin D, CD31, and P-glycoprotein, assessed on consecutive sections from the same frozen tissue samples. The results show that preserved E-cadherin expression correlates with high degree of tumour differentiation, low proliferative activity, and low expression of prognostic markers. The deregulation of E-cadherin is independent of other steps of tumour invasion, such as protease digestion of extracellular matrix and angiogenesis.
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PMID:E-cadherin quantitative immunocytochemical assays in breast carcinomas. 915 15

Conventionally, tumor size, axillary lymph nodes status, histologic type and grading, proliferative activity, steroid receptors have been used to predict the natural history of breast cancer. In node-negative patients with breast cancer it is most important to identify biological markers that can predict the risk of systemic relapse. These features have been used to allow selection of the best treatment. In this paper we describe the prognostic significance of new tumoral markers in breast cancer patients without axillary involvement. We analyze the prognostic role and the correlation with response to treatment of these parameters: ploidy, oncogenes, p53, epidermal growth factor receptor and cathepsin D.
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PMID:[Prognostic factors in breast carcinoma with negative axillary lymph nodes]. 920 16

Traditional and immunohistochemical markers of prognosis were examined in 455 mammary carcinomas derived from breast cancer screening and compared with those of 277 carcinomas presenting symptomatically over the same period. Tumours detected by population screening under the U.K. National Health Service Programme do not differ from those detected by other screening projects, but compared with symptomatic cancers, screen-detected cancers are more likely to be in situ and if invasive, to be smaller, of lower grade, and to have invaded vessels, perineural spaces, and lymph nodes less frequently. Tubular and cribriform types are more often represented in screened patients. Immunohistochemical markers which have been proposed as being related to likely tumour behaviour (epidermal growth factor receptor, c-erbB-2 protein, oestrogen and progesterone receptors, cathepsin D, p53, and retinoblastoma protein) do not distinguish screen-detected from 'clinical' cancers. It is concluded that cancers diagnosed at screening do not differ biologically from those presenting clinically, but are the same lesions detected at an earlier stage of their natural history.
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PMID:The pathological and biological nature of screen-detected breast carcinomas: a morphological and immunohistochemical study. 958 38

Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).
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PMID:Automated and quantitative immunocytochemical assays of Bcl-2 protein in breast carcinomas. 925 1


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