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)

Bax and Bcl2 are functionally antagonistic proteins which control apoptosis, whose expression in human tumours could be of prognostic value. We evaluated Bax and Bcl2 expression in 239 breast carcinomas (99 N0, 140 N1/2) with long term follow-up (median 79 months, range 11-140) in relation to clinico-pathologic parameters, clinical outcome, adjuvant therapy and expression of oestrogen receptor protein and p53. The prognostic value of Bax was investigated in the whole series of patients and in subgroups of homogeneously staged and treated patients (i.e., node-negative, N1/2 CMF-treated, N1/2 tamoxifen-treated). Bax immunostaining was cytoplasmic and heterogeneous. Cases were scored as Bax-positive if there were more than 20% reacting cells. High Bax expression was associated with positive nodal status (p = 0.03) and high Bcl2 expression (p = 0.01) and was more frequent in high-grade tumours. In the node-negative subgroup, Bax expression was associated with small tumour size. No association was seen with other parameters or with clinical outcome in any subgroup of patients. Since the apoptotic rate of a tumour is influenced by the ratio Bcl2/Bax, we investigated the combined effects of Bax and Bcl2 expression in relation to clinical outcome. However, no differences in survival were seen in the Bcl2-negative and Bcl2-positive groups when they were subdivided on the basis of the level of Bax expression and vice versa. In experimental systems, p53 is a direct transcriptional activator of the human bax gene. However, we could not observe any relation between Bax and p53 expression. We investigated whether the combined p53/Bax expression could have any prognostic value since it is predicted that tumours with normal p53 expression and concurrent high levels of Bax should be less aggressive and more susceptible to therapy. However, while p53 itself was of prognostic value, Bax expression was not related to prognosis in p53-negative or in p53-positive groups.
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PMID:Bax immunohistochemical expression in breast carcinoma: a study with long term follow-up. 949 51

The clinicopathologic features of 32 metaplastic carcinomas with heterologous osteocartilaginous elements are reported. Each neoplasm consisted of invasive adenocarcinoma accompanied by a cartilaginous or osseous component. In 10 neoplasms, this consisted of cartilage and in 2 the heterologous element was osteoid or bone exclusively. The remaining 20 neoplasms contained a mixture of cartilaginous and osseous components. All patients were women; mean age was 56 years. Twenty-four patients were treated using mastectomy and eight by local excision. Twenty-six patients underwent axillary lymph node dissection. Lymph node metastases were detected in 6 of the 26 (23%) patients who underwent axillary dissection. Clinical follow-up was available for 29 of 32 patients (91%). Local recurrence or distant metastases developed in 6 patients (21%) within 2 years of initial treatment, and 4 of these patients died of metastatic carcinoma. The overall 5-year survival rate was 60%. When compared with control patients with infiltrating duct carcinoma, the group with metaplastic carcinoma tended to have a more favorable prognosis after adjustment for nodal status and tumor size. The prognosis of patients with metaplastic mammary carcinoma with heterologous osteocartilaginous elements is dependent on tumor stage at diagnosis. Immunohistochemical studies for 34BE12, p53, retinoblastoma protein, HER/2neu (polyclonal), epidermal growth factor receptor, and cyclin D1 were performed in 18 cases. Positive immunohistochemical staining was found as follows: 34BE12: n = 13 (72%); p53: n = 11 (61%); retinoblastoma protein: n = 12 (66%); HER2/neu: n = 2 (11%); epidermal growth factor receptor: n = 7 (38%); and cyclin Dm: n = 5 (28%). Positive staining for 34BE12 was observed in the carcinomatous component in 5 (38%) of the neoplasms, in the metaplastic component in 2 (15%), and in both elements in 6 (64%). A p53 staining was observed in the carcinomatous component exclusively in 4 (36%) of 11 p53-positive tumors. No disparity in p53 staining was noted between the epithelial and metaplastic elements in the other p53-positive tumors. Expression of these markers did not correlate with clinicopathologic features such as patient age, tumor size, tumor type, relative proportion of metaplastic elements, and axillary nodal status and was not predictive of disease-free survival.
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PMID:Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. 950 Feb 19

Most recent decisions for breast cancer patients are made on the basis of prognostic and predictive factors. In addition to the traditional tumor/nodal/metastasis staging variables, estrogen and progesterone receptor status as assessed by biochemical ligand-binding assays are the only other factors that have been adequately validated and recommended for routine clinical use. Pathologists today, however, are evaluating estrogen and progesterone receptors almost exclusively by immunohistochemical means. Although many studies suggest that these tests might have equivalent or even superior abilities to predict patient outcome, there are important methodologic shortcomings to resolve before this technology achieves the clinical and technical validation necessary to justify its routine use. Many laboratories are also evaluating other factors for clinical use by immunohistochemical techniques, including, in particular, c-erbB-2, p53, and Ki-67 proliferation indices. Although available studies suggest that these factors might indeed be helpful in making treatment decisions, their clinical usefulness is still controversial, and, like the assessment of hormone receptors, there are important unresolved technical issues, such as how to prepare the tissue, which reagents to use and, most importantly, how to interpret the results. A few laboratories have gone to considerable effort to develop reproducible methods for evaluating these factors, and they have performed comprehensive studies demonstrating the prognostic and predictive significance of their results. Nonetheless, most laboratories offering these tests have not adequately validated them and might not even be aware of the issues needing attention. Unless laboratories validate their tests or follow the procedures of others who have, they run the risk of reporting meaningless and potentially harmful results. In the future, these and other factors will be incorporated into a prognostic index that will better reflect the biologic diversity of breast cancer and that will more accurately predict clinical outcome.
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PMID:Prognostic and predictive factors in breast cancer by immunohistochemical analysis. 950 86

Squamous cell carcinomas of the head and neck are a heterogeneous group of tumours with regard to anatomical site, natural history and response to various treatments. Assessment of the role of biomarkers as indicators of prognosis or response to treatment is thus complex. In the last decade, different biomarkers have been investigated in the search for objective and reproducible indicators of prognosis. In 69 squamous cell carcinomas of the oral cavity or oropharynx from patients treated with radical surgery alone, we determined cell kinetics, evaluated as in vitro 3H-thymidine labelling index (TLI), p53, bcl-2 and glutathione S-transferase pi (GST pi) expression, by using immunohistochemical methods. The biological variables were unrelated to one another or to established clinical and pathological prognostic factors. Univariate analysis showed that a low proliferative activity was associated to a significantly higher risk of death than that observed in patients with a high TLI, whereas p53, bcl-2 and GST pi expression did not provide prognostic information. Multivariate analysis showed that cell proliferation, gender and nodal status retained their clinical relevance. In the subset of node-negative patients, TLI and p53 expression were indicators of survival. Moreover, the combined analysis of TLI and p53 expression identified a subgroup of node-negative patients with slowly proliferating and highly p53-expressing tumours who died within 1 year of radical surgery. These results indicate that in patients with operable oral cavity and oropharyngeal cancer, biomarkers can provide important information on clinical outcome.
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PMID:Biological indicators of survival in patients treated by surgery for squamous cell carcinoma of the oral cavity and oropharynx. 950 24

ELAM is an E-Selectin adhesion molecule involved in the inflammatory process but it is also thought to potentially participate in the development of blood borne metastases, by facilitating tumour cell adhesion to vessels wall. ELAM expression in tumours was immunohistochemically investigated in 203 breast carcinomas. Frozen tissue sections were probed with monoclonal anti ELAM (Clone 1.2B6) using automated and quantitative immunoperoxidase systems. A positive anti-ELAM immunoreaction was observed in 113 tumours (57%). The mean surface of positive tumours varied from 3% to 50% (mean = 11.75%, SD = 8.7) and was correlated with histoprognostic indicators and tumour expression of various antigens detected according to the same method as ELAM. The results showed that ELAM immunoexpression was independent of the tumour size, grade and type and of the nodal status but significantly increased parallel to patients' age (p<0. 01). ELAM expression was independent of Ki-67/MIB1, anti-P53 and anti-Bcl2, anti-CD44v, anti-c-erbB-2, anti-CD31, anti-RE/RP, anti-PS2, and anti-VLA3 immunoreactions. But ELAM expression correlated with that of the VCAM vascular cell adhesion molecule (p=0.0004), VLA2 (p<0.0001), P-glycoprotein (p=0.025), and of Cathepsin D to a lower degree (p=0.06) and inversely correlated with E-cadherin (p=0.03). The results suggest that endothelial cell activation is independent of tumour cell proliferative activity and of stromal angiogenesis and that the precise role and regulation of ELAM in tumours remains to be elucidated. Also the clinical relevance of ELAM immunohistochemical expression requires further investigation and correlation with patients' follow-up.
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PMID:ELAM selectin expression in breast carcinomas detected by automated and quantitative immunohistochemical assays. 953 26

To validate the prognostic value of the determination of p53 expression, intratumoral microvessel density (IMD) (a measure of angiogenesis), and the conventional features, we studied 531 patients operated of breast cancer (271 node-positive and 260 node-negative), with a median follow-up exceeding 6 years. IMD was assessed by using the anti-CD31 antibody to identify the microvessels. p53, estrogen receptor (ER) and progesterone receptor (PgR) were determined by immunocytochemistry using the antibodies PAb1801, H-222 Sp2y and KD-68, respectively. The prognostic value of the markers was analyzed by univariate and multivariate statistical analyses. In the overall series p53 expression, IMD, nodal status, ER and PgR were statistically significant prognostic indicators for both relapse-free survival (RFS) and overall survival (OS) in the final multivariate model. Likewise, tumor size and menopausal status were significant prognostic indicators for RFS and OS, respectively. In the subgroup of node-negative patients who did not receive adjuvant therapy only p53, IMD, and tumor size were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant chemotherapy, IMD, the number of involved nodes and PgR were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant tamoxifen, IMD and ER (and the number of involved nodes, only for OS) were statistically significant for both RFS and OS in the final multivariate model. Different markers played a diverse prognostic role in the diverse subgroups studied. Angiogenesis was the sole marker which retained prognostic value in all the sub-groups analyzed. p53 retained significance only in the subgroup of node-negative patients, whilst ER and PgR were statistically significant in the subgroups of node-positive patients treated with adjuvant hormone therapy or chemotherapy, respectively.
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PMID:Prognostic significance of p53, angiogenesis, and other conventional features in operable breast cancer: subanalysis in node-positive and node-negative patients. 953 38

The tumour-suppressor gene TP53 is frequently mutated in breast tumours, and the majority of the mutations are clustered within the core domain, the region involved in DNA binding. We searched for alterations in this central domain of the TP53gene in 222 human breast cancer specimens using polymerase chain reaction-single-strand conformation analysis (PCR-SSCA) followed by sequencing. TP53 gene mutations were observed in 66 tumours (31%), including three tumours that contain two mutations. Fifty-four (78%) of these mutations were missense point mutations, one was a nonsense mutation and four were deletions and/or insertions causing disruption of the protein reading frame, whereas four mutations were either silent or a polymorphism (at codon 213; n = 6). Interestingly, the majority of missense mutations were observed at codon 248. The outcome has been related with patient and tumour characteristics, and with prognosis in 177 patients who were eligible for analysis of both relapse-free and overall survival (median survival for patients alive was 115 months). There was no significant association between the frequency of TP53 mutations and menopausal or nodal status, or tumour size. In a Cox univariate analysis, TP53 gene mutation was significantly associated with poor relapse-free survival (RFS: P = 0.02) but not with overall survival (OS: P = 0.07). In a Cox multivariate analysis, including classical prognostic factors, TP53 gene mutation independently predicted poor RFS and OS (RHR = 1.8 and 1.6 respectively). Unexpectedly, the median relapse-free survival of patients with a polymorphism at codon 213 or with a silent mutation was shorter (median 11 months) than the median relapse-free survival of patients with or without a TP53 gene mutation (median 34 or 48 months respectively). In an exploratory subset analysis, mutations in codons that directly contact DNA were related with the poorest relapse-free (P < 0.05) and overall survival (P < 0.02). These data imply that in the analysis of the prognostic value of TP53, the type of mutation and its biological function should be considered.
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PMID:Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer. 956 50

Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma. We describe eight cases of B-cell extranodal non-Hodgkin's lymphoma occurring during the course of chronic HCV-related hepatic disease (low-grade of mucosa-associated lymphoid tissue [MALT]-type; diffuse large cell; Burkitt; diffuse small cell). Some were localized to the liver (2), liver and spleen (1), spleen (1), peritoneal cavity (1), parotid gland (1); others manifested in the nasopharynx (1) and eyelid (1) but were accompanied by nodal disease. Four lymphomatous specimens available for molecular analysis exhibited clonal immunoglobulin gene rearrangements, lacked bcl-2, bcl-6, c-myc genes and p53 alterations, and did not contain replicative intermediate HCV RNA, as documented by a strand-specific reverse transcriptase-polymerase chain reaction. Low levels of positive-strand HCV RNA were detected in a single hepatic lymphoma, suggesting the presence of the virus in residual hepatocytes. The antigen-driven properties of HCV-associated B-cell malignant neoplasms may be considered for hepatic MALT-type lymphoma, which probably originated from lymphoid tissue acquired during long-standing HCV infection.
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PMID:Extranodal lymphomas associated with hepatitis C virus infection. 957 65

To characterize the biological features of breast cancer associated with germ-line mutations in BRCA1 and BRCA2, invasive tumors were studied from 58 Jewish women ascertained through studies of early-onset breast cancer. All women were tested for the BRCA1 founder mutations 187delAG (commonly known as 185delAG) and 5385insC (commonly known as 5382insC) and the BRCA2 founder mutation 6174delT. Mutations were detected in 17 of 58 (29.3%) women. Comparing BRCA-associated breast cancers (BABCs) to cases arising in women without founder mutations, no differences were noted in tumor size, tumor stage, or frequency of axillary nodal involvement. Infiltrating ductal carcinoma was the predominant histological type in both groups. BABCs were significantly more likely to be of histological grade III (100 versus 63%; P = 0.04), estrogen receptor negative (75 versus 35%; P = 0.004), and HER2/neu negative (87 versus 58%; P = 0.04). An associated intraductal component was present in 59% of BABCs and 76% of cancers not associated with mutations (P = not significant). A high Ki-67 labeling index was more commonly observed in BABCs than in cases without mutations (83 versus 48%; P = 0.09). There were no differences between the two groups in the frequency of expression of epidermal growth factor receptor, cathepsin D, bcl-2, p27, p53, or cyclin D. There were no significant differences in relapse-free or overall survival. These observations suggest that breast cancers arising in Jewish women with germ-line BRCA founder mutations have a greater proliferative potential than cancers in women without such mutations. Additional studies of BABC are required to determine the nature and implications of additional genetic abnormalities occurring in these tumors.
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PMID:BRCA-associated breast cancer: absence of a characteristic immunophenotype. 958 22

The prognostic significance of Ki-67, p53, and Bcl-2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavidin-biotin method. Univariate survival analysis showed that a Ki-67 labeling index (Ki-67 LI) of > or = 8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P < 0.001). furthermore, a Ki-67 LI of > or = 8.7 in the nodal metastatic tumor was also associated with a poorer prognosis (P < 0.01). Multivariate analysis showed that the Ki-67 LI of primary tumors (P < 0.01) and lymph node metastases (P < 0.01) had independent prognostic value. p53 and Bcl-2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki-67 LI has more prognostic value than p53 and Bcl-2 expression for patients with prostate cancer that has spread to the lymph nodes.
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PMID:Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: a retrospective immunohistochemical analysis. 958 63


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