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

The prognostic and predictive role of p53 overexpression in breast cancer samples is usually investigated by using molecular biology or immunohistochemical methods. However, the results are to date controversial, and this is in part due to the methodological pitfalls of both the methods. To study the possibility of overcoming, at least in part, these problems we evaluated a commercially available chemiluminescent immunoassay with which the p53 concentrations of 220 specimens from node negative breast cancer were determined. The assay showed good analytical performance and found detectable levels in 84.7% of cases (median 0.22 ng/mg of proteins, range 0-50 ng/mg of proteins). p53 has been found inversely correlated with estrogen receptors and directly correlated with cathepsin D. The prognostic role of p53 was evaluated in two different ways: a) two previous studies (Borg et al 1995, DeWitte et al. 1996) using the same method found almost 30% of samples had significantly shorter DFS and OS. We subdivided our cases in order to identify the same positivity rate and to verify if the previous cathegorizations were effective also in our patient series. We confirmed the independent association with DFS (p = 0.006) and OS (p = 0.0005); b) considering that any categorization of quantitative parameters could cause a loss of clinical information, we also evaluated p53 as a continuous variable. Multivariate analysis showed a significant quantitative relationship between p53 and both disease free (p = 0.026) and overall survival (p = 0.02).
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PMID:Quantitative chemiluminescent immunoassay of p53: prognostic significance in 220 node-negative breast cancer tissue. 949 90

Tumor biological factors uPA, PAI-1, cathepsin D, S-phase fraction (SPF), MIB1 (Ki-67), p53, and HER-2/neu were assessed in 100 node-negative breast cancer patients. Their prognostic impact on disease-free (DFS) as well as overall survival (OS) was compared to that of traditional factors tumor size, grading, and steroid hormone receptor status. Antigen levels of uPA, its inhibitor PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. SPF was determined by flow cytofluorometry, MIB1, p53, and HER-2/neu by immunohistochemistry in adjacent routinely formalin-fixed paraffin sections. Median follow-up in all patients still alive at time of analysis was 76 months. Univariate analysis determined PAI-1 (p = 0.0001), uPA (p = 0.0437), MIB1 (p = 0.0214), and SPF (p = 0.0248) as statistically significant prognostic factors for DFS. In contrast, tumor size, steroid hormone receptor status, grading, p53, HER-2/neu, and cathepsin. D failed to be of prognostic value. In multivariate analysis, including the statistically significant prognostic factors PAI-1, uPA, MIB1, and SPF, only PAI-1 (p = 0.0003, relative risk: 4.7) proved to be of independent statistical significance for DFS. Regarding OS, PAI-1 was the only statistically significant prognostic factor in univariate (p = 0.0001) as well as multivariate analysis (p = 0.0000, relative risk: 7.1). Thus, factors describing the invasive and metastatic capacity of tumor cells (uPA, PAI-1) and factors related to their proliferative activity (SPF, MIB1) provide valuable prognostic information in node-negative breast cancer patients.
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PMID:Prognostic impact of tumor biological factors on survival in node-negative breast cancer. 970 82

Cervical cancer is the most common cancer among women in South India. More than 70% of the cases present in stage IIB and IIIB and of these more than 50% fail conventional treatment. The purpose of the present study was to determine the prognostic significance of Bcl-2 and p53 expression in squamous cell carcinomas of the cervix. Using immunohistochemistry, 40 cases of stage IIB and IIIB squamous cell carcinomas of the cervix treated with radiotherapy were studied for the expression of Bcl-2 and p53 protein and their prognostic value ascertained. Bcl-2 was expressed in 65% (n=26) of the tumours. There was a statistically significant association (p=<0.025) between Bcl-2 expression and poorer DFS and OS in stage IIB cases. In stage IIIB, these associations were not obvious probably due to additional genetic events overshadowing the significance of Bcl-2 expression. Only 4/40 (10%) of the cases were positive for p53 protein expression and there was an inverse correlation between p53 expression and Bcl-2 expression. This study suggests that Bcl-2 can be a useful marker to identify the poor prognostic group in stage IIB cases and needs to be confirmed in a larger series.
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PMID:Prognostic significance of Bcl-2 and p53 protein expression in stage IIB and IIIB squamous cell carcinoma of the cervix. 1021 40

Factors reflecting two major aspects of tumour biology, invasion (urokinase-type plasminogen activator (uPA), plasminogen activator inhibiter (PAI-1), cathepsin D) and proliferation (S-phase fraction (SPF), Ki-67, p53, HER-2/neu), were assessed in 125 node-negative breast cancer patients without adjuvant systemic therapy. Median follow-up time was 76 months. Antigen levels of uPA, PAI-1 and cathepsin D were immunoenzymatically determined in tumour tissue extracts. SPF and ploidy were determined flow-cytometrically, Ki"'-67, p53, and HER-2/neu immunohistochemically in adjacent paraffin sections. Their prognostic impact on disease-free (DFS) and overall survival (OS) was compared to that of traditional factors (tumour size, grading, hormone receptor status). Univariate analysis determined PAI-1 (P < 0.001), uPA (P = 0.008), cathepsin D (P = 0.004) and SPF (P = 0.023) as significant for DFS. All other factors failed to be of significant prognostic value. In a Cox model, only PAI-1 was significant for DFS (P < 0.001, relative risk (RR) 6.2). In CART analysis for DFS, the combination of PAI-1 and uPA gave the best risk group discrimination. For OS, PAI-1, cathepsin D, tumour size and ploidy were statistically significant in univariate, but PAI-1 was the only independently significant factor in Cox analysis (P < 0.001, RR 8.9). In particular, this analysis shows that PAI-1 is still a strong and independent prognostic factor in node-negative breast cancer after extended 6-year median follow-up.
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PMID:Risk-group discrimination in node-negative breast cancer using invasion and proliferation markers: 6-year median follow-up. 1040 48

About 40% of patients with colorectal carcinoma will develop local or distant tumour recurrences. Integrated analyses of bio-pathological markers, predictive of tumour aggressiveness, may offer a more rational approach to planning adjuvant therapy. To this end, we analysed the correlation between p53 accumulation, Bcl-2 expression, DNA ploidy, cell proliferation and conventional clinico-pathological parameters by testing the prognostic significance of these variables in a series of 171 colorectal carcinoma patients with long-term follow-up. The relationships among the various bio-pathological parameters, analysed by multiple correspondence analysis, showed 2 different clinico-biological profiles. The first, characterised by p53 negativity, Bcl-2 positivity, diploidy, low percentage of cells in S-phase (%S-phase), a low Ki-67 score, is associated with Dukes' A-B stage, well differentiated tumours and lack of relapse. The second, defined by p53 positivity, Bcl-2 negativity, aneuploidy, high %S-phase and elevated Ki-67 score, correlates with Dukes' C-D stage, poorly differentiated tumours and presence of relapse. When these parameters were examined according to Kaplan-Meier's method, significantly shorter disease-free (DFS) and overall survival (OS) were also observed in patients bearing p53 positive and Bcl-2 negative tumours, in Dukes' B stage. In multivariate analysis, p53 accumulation and Bcl-2 expression emerged as independent predictors of a worse and better clinical outcome, respectively. Our results indicate that, in colorectal adenocarcinomas, a biological profile, based on the combined evaluation of p53 and Bcl-2, may be useful for identifying high risk patients to be enrolled in an adjuvant setting, mainly in an early stage of the disease. Int. J. Cancer (Pred. Oncol.) 84:545-552, 1999.
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PMID:Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2. 1056 96

Steroid receptor analysis is the only widely accepted prognostic/predictive marker in breast cancer (BC) treatment. In the present study we evaluated the prognostic role of ER/PgR with p53 and Bcl2, in a series of 277 BC (153 pN1/2, 122 pNO, 2 pNx) with a long-term follow-up (67 months for DFS, 75 months for OS). Our results, besides confirming the usefulness of ER immunohistochemical expression as a prognostic marker, showed that PgR expression alone had a borderline/not significant prognostic value in the whole series (p=0.08 for DFS and p=0.09 for OS), while showed to be prognostic in N+ cases (p=0.02 for DFS and p=0.03 for OS). PgR prognostic value, however, was not independent at the multivariate analysis. By combining ER with PgR, p53 and Bcl2, we showed that ER/p53 and ER/Bcl2 phenotypes had a better discriminant role than ER/PgR phenotype. The ER+/p53+ phenotype was at higher risk of relapse/death as compared with ER+/p53- phenotype. Conversely ER-/p53+ phenotype showed the most unfavourable prognosis. Similar results could be observed concerning ER/Bcl2 phenotypes. Our study showed that the combined evaluation of ER/PgR weakly enhanced the prognostic/predictive power of ER status alone. On the contrary, the combined evaluation of ER/p53 and ER/Bcl2, improved this prognostic/predictive capability and allowed the separation of ER positive and ER negative cases into subgroups with different prognosis.
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PMID:Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up. 1056 20

Breast cancer heterogeneity can be related directly to its variability at the genetic level. Thus, tumor genotyping could be a valuable approach to define breast tumor subtypes. It has been shown that it is possible to delineate subgroups of breast tumors according to specific sets of DNA amplifications. The aim of the present work was to study the prognostic significance of these DNA amplifications. We studied DNA amplification at eight genes or loci (AIB1, CCND1, EMS1, ERBB2, FGFR1, MDM2, MYC, and RMC20C001) as well as p53 mutations in a series of 640 breast cancer patients who had not received presurgical therapy and analyzed the correlations with survival DNA amplification was assessed by Southern blotting and was scored positive when exceeding three to five copies. Mutations in the p53 gene were searched by four-color fluorescent single. strand conformational polymorphism, using an automated sequencer. Of the nine genetic alterations tested, four (CCND1, EMS1, FGFR1, and p53 mutations) showed a significant association with reduced disease-free (DFS) and/or overall survival (OVS) in the unselected set of patients by univariate test. Correlations for p53 were found only when selecting mutations in exons 5 or 7. Analysis of node-negative and -positive subgroups of patients showed that MDM2 amplification and p53 mutations bore prognostic significance in node-negative patients, whereas amplification of CCND1, EMS1, and FGFR1 correlated with poor outcome in node-positive patients. Multivariate analysis on an unselected set of patients retained significance for the amplification of EMS1, FGFR1, and MDM2 with DFS, of CCND1 with OVS, and of RMC20C001 with both DFS and OVS. Interestingly, stratified analysis according to nodal status confirmed results obtained in the univariate tests: significance of MDM2 amplification and p53 mutations in node-negative and that of CCND1, EMS1, and FGFR1 in node-positive patients. We also observed an association between the number of genetic alterations observed in a tumor and poor prognosis. Patients with two or more amplified loci had a worsened outcome. Strongly correlating coamplifications such as CCND1 and FGFR1, as well as ERBB2 and MYC, were associated with a significant reduction of patient survival, thus indicating cooperative effects. Our data support the idea that genetic alterations in breast cancer are not only helpful for phenotyping purposes, but can also represent powerful prognostic indicators in the clinical practice.
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PMID:Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations. 1070 27

The prognostic values of p53 and of its downstream mediator p21WAF1/Cip1 in patients receiving adjuvant chemotherapy for epithelial ovarian cancer have not been clearly established. Tumor extracts from a series of 120 patients treated postsurgically with cisplatin or carboplatin alone or together with other chemotherapeutics for primary ovarian carcinoma were assayed both for p53 protein by an immunofluorometric assay developed by us and for p21 protein by a commercially available immunoassay. Relative risks (RRs) for cancer relapse and death after 24 months of follow-up were determined by multivariate Cox regression analysis. Disease-free (DFS) and overall survival (OS) probabilities were also examined by the Kaplan-Meier method and log-rank tests. All other procedures were similarly nonparametric and based on two-sided tests of significance. Concentrations of p53 were elevated in patients with advanced stage disease (P = 0.02) or poorly differentiated (P = 0.03), suboptimally debulked tumors (P = 0.02), as well as in patients who failed to respond to chemotherapy (P = 0.03), as assessed by computed tomography scanning, serum CA125 determination, and second-look laparotomy. Statistically significant associations between concentrations of p53 and p21 were not found, nor were relationships demonstrated between concentrations of p21 and other clinicopathological variables or treatment response. Univariate analysis showed that p53 concentrations above the median indicated significantly higher risks for relapse (P = 0.04) and death (P < 0.01) and showed trends for increasing risks for relapse (P = 0.04) and death (P < 0.01) when p53 was considered as a four-level categorical variable. Multivariate analyses adjusted for age, stage, grade, and residual tumor size confirmed these observations (RR = 1.50; P = 0.05 for DFS and RR = 1.92; P = 0.03 for OS) for median-dichotomized p53, but the trends were of borderline significance (P = 0.09 for DFS and P = 0.07 for OS). In contrast, p21 positivity was not a significant predictor of favorable outcome in univariate survival analysis, and use of a three-level variable combining positivity or negativity status for both p53 and p21 did not yield greater separation of patients into risk groups (P = 0.07 for DFS and P = 0.06 for OS) than the use of p53 alone. Assessment of p53 expression may be an independent indicator of poor prognosis in ovarian cancer patients treated with adjuvant chemotherapy. The prognostic value of p21 expression, however, could not be demonstrated in our series of ovarian cancer patients.
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PMID:Evidence for a dose-response effect between p53 (but not p21WAF1/Cip1) protein concentrations, survival, and responsiveness in patients with epithelial ovarian cancer treated with platinum-based chemotherapy. 1095 12

Our objective was to investigate the prognostic significance of cell turnover (apoptosis and proliferation) in breast cancer patients. Apoptosis was microscopically quantitated on histological sections from 791 breast cancer patients with long-term follow-up (median, 16.3 years). Apoptotic counts were also compared with proliferation data (mitotic counts and MIB-1 labeling); apoptosis data derived from terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay; and pathobiological variables, including p53, erbB-2, and estrogen receptor (ER). High apoptotic counts were associated with increased cellular proliferation, ER negativity, immunopositivity of erbB-2 and p53 (P < 0.0001), and shortened disease-specific survival (DSS; P = 0.0009) and disease-free survival (DFS; P = 0.0006). Other factors associated with shortened DFS and DSS by univariate analysis were high tumor grade, nodal metastases, and large tumor size (P < 0.0001 for each). Multivariate analysis of data for all of the patients demonstrated that tumor size, nodal status, ER, histological grade, and erbB-2 showed independent prognostic value. In node-negative patients, tumor size and mitotic rate per 1000 cells independently predicted DFS (P = 0.0055). Tumor grade was the only independent predictor of DSS. For node-positive patients, tumor size, nodal status, ER, and erbB-2 were independent prognostic factors. The number of mitoses per 1000 was independently associated with DFS (P = 0.043) but not with DSS. Apoptosis data did not provide independent prognostic value in any, node-positive or node-negative, breast cancer patients.
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PMID:Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. 1141 May 11

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is an enzyme that catalyzes the reversible dephosphorylation of thymidine, deoxyuridine and their analogs. TP has also angiogenic properties, although the precise mechanism by which it promotes angiogenesis is not known. We examined TP expression using immunohistochemistry (654-1 Mab) in 182 invasive breast carcinomas (67 N0 and 115 N1/2; median follow-up 78 months [range, 3-177]; 51 patients treated with adjuvant systemic cyclophosphamide, methotrexate and 5-fluorouracil [CMF] chemotherapy and 82 with tamoxifen). High TP expression was found in 142 cases (78%) and correlated with lower histologic grade and low p53 expression. No correlation was found between TP expression and vascular density. TP-positive tumors had a significant increase in both disease-free survival (DFS; p = 0.0025) and overall survival (OS; p = 0.0070) in the total cohort of patients and in the subgroups of node-positive patients and patients treated with CMF adjuvant therapy; no significant difference in either DFS or OS was observed in patients without CMF treatment. Our findings suggest that TP has little effect on tumor angiogenesis of breast carcinoma, whereas it could represent an interesting marker that could predict response to CMF chemotherapy.
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PMID:Prognostic value of thymidine phosphorylase expression in breast carcinoma. 1180 15


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