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)

In order to assess the specificity of biotinylated anti-c-erbB-3 antibody, screening was performed on a series of tumour cell lines and lymphocytes. Staining was found to be consistent, with good reproducibility. Twenty-nine consecutive breast cancer samples were obtained from women treated with tamoxifen and undergoing elective mastectomy. Twenty-eight invasive ductal carcinomas and 1 DCIS were stained for c-erbB-3 expression: 2 were grade I (Bloom and Richardson), 15 grade II, and 11 grade III tumours, 1 being unclassified; 16 were axillary node positive and 10 node negative; in 2 cases no nodes were sampled. Tumours examined by flow cytometry were stained with cytokeratin FITC antibody and the cytokeratin-positive population gated. Using Mann-Whitney analysis no association was seen between c-erbB-3 expression and Bloom and Richardson grade or axillary node status. In the tumour samples c-erbB-3 expression was found to show as association with EGF-R (P = 0.021 r2 = 0.16), PgR (P = 0.02, r2 = 0.16), c-myc (P < 0.0001, r2 = 0.5), c-jun (P = 0.001, r2 = 0.4) and c-fos (P = 0.001, r2 = 0.5) but not with c-erbB-2 (P = 0.2, r2 = 0.06), ER (P = 0.4, r2 = 0.02) or p53 1801 (P = 0.05, r2 = 0.2). Expression of c-erbB-3 may not be an independent marker of prognosis, but it is associated with other markers of poor prognosis and early cellular events linked with aberrant growth and differentiation.
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PMID:A flow cytometric study of c-erbB-3 expression in breast cancer. 853 73

The prognosis of patients with Stage I and II non-small cell lung cancer (NSCLC) can be estimated but cannot be definitively ascertained by use of current clinicopathologic criteria and tumor marker studies. The potential value of probabilistic neural networks (NNs) with genetic algorithms and multivariate logistic regression to predict the survival of NSCLC patients has not been previously evaluated. Multiple prognostic factors (age, sex, cell type, stage, tumor grade, smoking history, and immunoreactivity to c-erbB-3, bcl-2, Glut1, Glut3, retinoblastoma gene and p53 were correlated with 5-year survival in 63 patients with Stage I or II NSCLC, treated solely by surgical excision at Baylor Medical College, Houston, Texas. Several probabilistic NNs with genetic algorithm models were developed using the prognostic features as input neurons and survival at 5 years (free of disease/dead of disease) as output neurons. The probabilistic NN yielded excellent classification rates for dependent variable survival. The best model was trained with 52 cases and classified all 11 "unknown" test cases correctly. Several statistically significant logistic regression models were fitted using 50 cases to build the models and 13 cases as "hold-out" test cases. These multivariate statistical models provide various cutoff values that predict/classify the probability of survival at 5 years. In conclusion, probabilistic NNs and logistic regression models can be useful in estimating the prognosis of patients with Stage I and II NSCLC using multiple clinicopathologic and molecular variables. These multivariate predictive models need to be validated with much larger groups of patients to assess their potential clinical value.
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PMID:Artificial neural networks and logistic regression as tools for prediction of survival in patients with Stages I and II non-small cell lung cancer. 968 82

There is scant information on the cell proliferation, apoptosis, oncogenes, and tumor suppressor genes status in adenosis. Forty-eight foci of adenosis were studied with immunohistochemistry for MIB-1; c-erbB-2, c-erbB-3, bcl-2 oncogenes; and p53. To evaluate apoptosis, the TdT dUTP nick end labeling (TUNEL) method was applied. Results were compared with the same studies on benign prostatic hyperplasia (BPH) (n = 20), low-grade prostatic intraepithelial neoplasia (PIN) (n = 10); high-grade PIN (n = 20), Gleason sum 2 to 6 cancer (n = 16); and Gleason sum 7 to 10 cancer (n = 22). MIB-1 proliferation index was lowest in BPH, followed by adenosis, low-grade prostatic intraepithelial neoplasia (PIN), low-grade cancer, high-grade PIN, and high-grade cancer. The apoptotic rate was generally low in all groups, although it was higher in PIN and cancer. In BPH and adenosis, bcl-2 was absent in luminal cells. In low- and high-grade PIN, both basal and luminal cells expressed bcl-2, whereas in cancer, expression was found in only 1 case (3%). C-erbB-2 showed absent or low values for cancer and adenosis, whereas it was commonly expressed in BPH and low- and high-grade PIN. Low expression in adenosis was also found with c-erbB-3 (6%) compared with all other groups. Expression of p53 was confined to cancer. Despite a significantly higher proliferation index rate compared with BPH, adenosis showed a markedly lower proliferating index when compared with low-grade PIN, high-grade PIN, and cancer. Expression of the oncogenes c-erbB-2 and cerbB-3 was very low in adenosis, and the staining pattern for bcl-2 was similar to that of BPH. These results provide additional evidence to that of prior studies that adenosis is a histological small acinar proliferation more akin to BPH than high-grade PIN or adenocarcinoma.
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PMID:Cell proliferation, apoptosis, oncogene, and tumor suppressor gene status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer. 1049 43

The calcium-binding protein S100A4 is capable of inducing metastasis in rodent models for breast cancer. We now show that rabbit antibodies to recombinant rat S100A4 recognize specifically human S100A4 using Western blotting techniques and use them to assess the prognostic significance of S100A4 in primary tumors from a group of 349 patients treated between 1976 and 1982 for stage I and stage II breast cancer. The antibody stains normal breast tissue heterogeneously, but stains positively 41% of the carcinomas, leaving the remaining 59% as negatively stained. In addition to the carcinoma cells, some host stromal cells and lymphocytes are also stained, but these have been discounted in subsequent analyses. There is an association of staining of carcinomas for S100A4 with some tumor variables considered to be associated with poor prognosis for patients: tumor present in axillary lymph nodes (borderline P = 0.058), staining for c-erbB-3 (P = 0.002), cathepsin D (P = 0.024), and c-erbB-2 (P = 0.048). The association of staining for S100A4 with patient survival has been evaluated using life tables and analyzed using generalized Wilcoxon statistics. Eighty percent of the S100A4-negative patients but only 11% of the S100A4-positive patients are alive after 19 years of follow-up, and this association is highly significant (P < 0.0001); the former have a median survival of >228 months and the latter 47 months. The other tumor variables that show significant association with survival time are nodal status (P < 0.0001), tumor size (P = 0.0035), histological grade (P = 0.013), staining for c-erbB-2 (P = 0.0015), estrogen receptor (P = 0.028), and p53 (P = 0.032). Analysis of the association of patients with carcinomas staining for S100A4 and their survival in subgroups defined by these other tumor variables shows that in each subgroup, staining for S100A4 is associated with poorer survival. Patients whose tumors stain for S100A4 and possess involved lymph nodes (P < 0.0001), which are fixed to the chest wall (P = 0.015) or which stain for c-erbB-2 (P = 0.050), show a significant reduction in survival times over those with only S100A4-staining tumors. Patients with involved lymph nodes, or staining for c-erbB-2 in the S100A4-negative group fail to show any significant reduction in survival times. Multivariate regression analysis for 137 patients shows that staining for S100A4 is most highly correlated with patient deaths (P < 0.0001), but involved lymph nodes (P = 0.001), fixed tumors (P = 0.0002), and high histological grade (P = 0.022) are also significant independent prognostic variables. These results suggest that in this group of patients, the metastasis-inducing protein S100A4 is most tightly correlated with patient demise.
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PMID:Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer. 1074 28

Our aim was to compare the occurrence and prognostic significance over 14-20 years of immunocytochemically detected S100A4 and other tumour variables in primary tumours from 349 patients with operable breast cancer. For a cut-off of 1% staining of the malignant cells, the antibody to S100A4 stains positively 56% of the carcinomas. There was a significant association of staining for S100A4 with tumours fixed to the chest wall, staining for c-erbB-2, c-erbB-3, pS2, cathepsin D and, inversely, at borderline levels with staining for estrogen receptor. Using Wilcoxon statistics in univariate analyses, staining for S100A4, nodal status, tumour class, histological grade and staining for c-erbB-2, p53 were associated negatively and staining for estrogen receptor, progesterone receptor were associated positively with patient survival times. The survival times of patients with S100A4-negative carcinomas with or without one of the other tumour variables showed no significant differences, whilst those of patients with S100A4-positive carcinomas showed significant differences in a negative or a positive way. Multivariate regression analysis for 137 patients showed that staining for S100A4 is most highly correlated with patient deaths, but involved lymph nodes, fixed tumours, high histological grade and staining for progesterone receptor were also significant independent prognostic variables. Our results suggest that in this set of patients, the tumour variable most tightly correlated with patient death is S100A4.
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PMID:Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer. 1075

The expression of EGFR family members was examined by immunohistochemistry in 22 phyllodes tumors, and the results were evaluated together with immunohistochemical findings for proliferation markers Ki67 and BM28, and the tumor suppressor gene product p53. Light and electron microscopy were performed in all cases. Clinical information was obtained from the medial records. We did find that expression of EG FR, c-erbB-3 and c-erbB-4 proteins could be detected in the neoplastic mesenchymal cells, and that the expression increased with increasing malignancy. Increased expressions of Ki67, BM28, p53 and EGFR family members in neoplastic cells were associated with malignancy and unfavorable clinical course. Furthermore, the expression of ER-alpha and PR in the epithelial cells of phyllodes tumors was increased compared to that in normal breast epithelium. Finally, the application of electron microscopy helped to identify a group of malignant tumors, revealing neoplastic cells with characteristic nuclear indentations, as well as an increasing number of myofibroblasts.
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PMID:Phyllodes tumor of the breast: EGFR family expression and relation to clinicopathological features. 1120 34

The type I family of growth factor receptors is known to play a role in the development of several carcinomas, but its role in hepatic malignancies is not clearly understood. In this study we investigated the expression of this family of EGF-R, c-erbB-2, c-erbB-3 and c-erbB-4 in 38 intrahepatic cholangiocellular carcinomas (CCC) by means of immunohistochemistry. EGF-R expression was related to lymph node metastasis, aberrant p53 expression, proliferating activity, and carcinoma differentiation. c-erbB-2 expression was observed in more than 50% of the cases, but was not related to any clinicopathological features, c-erbB-3 expression was linked to lymph node metastasis, and c-erbB-4 expression was directly related to proliferating activity and lymph node metastasis. These results indicate that: 1) EGF-R contributes greatly to CCC progression, and c-erbB-3 and c-erbB-4 have roles similar to but less than that of EGFR, and 2) c-erbB-2 is expressed in CCC in high incidence, but its clinical role in CCC remains unclear.
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PMID:Expression and clinical significance of the erbB family in intrahepatic cholangiocellular carcinoma. 1126 24

The adhesive glycophosphoprotein (OPN) is capable of inducing metastasis in rodent models ofbreast cancer. We now show that a monoclonal antibody to rat OPN recognizes specifically human OPN using Western blotting techniques andused it to assess the prognostic significance of OPN in primary tumors of a group of 333 patients treated between 1976 and 1982 for operable stage I and stage II breast cancer. The antibody stains immunocytochemically normal breast tissue weakly but pregnant/lactating tissue and 66% of the carcinomas strongly, leaving the remaining 34% as negatively stained. In addition to the carcinoma cells, some host reactive stromal cells, macrophages, lymphocytes, and blood vessels are also stained, but these have been excluded in the following analyses. There is a significant association of staining of carcinomas for OPN with some tumor variables reported previously to be associated with patient outcome: high histological grade (P = 0.024), staining for c-erbB-3 (P < 0.001), p53 (P = 0.014), pS2 (P = 0.025), and borderline significance for progesterone receptor (P = 0.089). The association of staining for OPN with survival times of the patients has been evaluated using life tables over 14-20 years of follow-up (mean 16 years) and analyzed using generalized Wilcoxon statistics. Of the patients who have been classified as OPN-negative, 94% are alive, but only 26% of those classified as OPN-positive are alive after 19 years of follow-up. This association is highly significant (P < 0.0001); the former have a median survival of >228 months and the latter 68 months. When the patients are divided into separate classes based on the percentage of carcinoma cells staining for OPN, the five classes show a progressive decrease in survival with increasing percentage of stained carcinoma cells, and this association is also highly significant (P < 0.0001). Other tumor variables that show a significant association with patient survival times in this group of patients include nodal status, tumor size, histological grade, staining for c-erbB-2, estrogen receptor alpha, or p53. Analysis of the association of patients with carcinomas staining for OPN and their survival in subgroups defined by these tumor variables shows that positive staining for OPN in each subgroup is associated with poorer survival. There is little difference in patient survival times in the OPN-negative group of patients with or without any of the other tumor variables examined. Multivariate regression analysis for 202 patients shows that staining for OPN is most highly correlated with patients' deaths (P < 0.0001), but involved lymph nodes (P = 0.0007), fixed tumors (P = 0.0008), and staining for estrogen receptor alpha (P = 0.008) are also significant independent prognostic variables with that for c-erbB-2 being of borderline significance (P = 0.060). These results suggest that in this group of patients, the presence of the metastasis-associated protein OPN is tightly correlated with patient demise.
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PMID:Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. 1206 84

The frequency of increased EGFR-mRNA expression was determined in 57 patients suffering from NSCLC by applying quantitative real-time PCR. The findings were correlated with clinical parameters and the immunohistochemical (IHC) markers EGFR, c-erbB-2, c-erbB-3, Ki-67 and p53 on cryostat sections. Of the patients 46% showed increased EGFR-mRNA, 35% revealed an increased IHC-EGFR expression; 16% of the patients showed a combined positivity and 35% a combined negativity when applying both methods, and 17 (30%) of the cases revealed increased EGFR-mRNA without IHC-EGFR expression. This subgroup was characterised by p53 coexpression and the highest frequency of deaths (35% vs. 20%) indicating a more aggressive tumour type. In contrast to IHC - where positivity was seen predominantly in squamous cell carcinomas (48% vs. 27%) - EGFR-mRNA expression was observed equally in both histological subtypes (48% vs. 43%). PCR-EGFR and IHC-EGFR tumour typing identifies different tumour characteristics with different clinical courses. Whether this combined typing could help to identify patients who respond to anti-EGFR therapies is worth further testing.
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PMID:Characterisation and predictive value of epidermal growth factor receptor status using quantitative real-time PCR combined with immunohistochemistry on non-small cell lung cancer specimens. 1296 67

A real-time PCR technique with automated computerized analysis (TaqMan ) was tested to detect K-ras mutations in 66 patients suffering from NSCLC. This technology is characterized by high reproducibility of data and a time-saving analysis procedure. In 11% (7/66) of the tumour specimens and 2% (1/58) of adjacent tumour-free lung specimens a K-ras codon 12 mutation was detected. In adenocarcinomas containing > or =40% tumour cells, however, K-ras mutations were seen in 25% of the cases. The point mutations detected in tumours were GGT right curved arrow TGT in five cases and GGT right curved arrow GTT in two cases. As compared with immunohistochemical parameters, the K-ras mutated group was characterized by a c-erbB-2 negativity (p=0.04) and a smaller number of c-erbB-3 (p=0.02) positive cases. EGFR, bcl-2, p53, Ki-67 and p120 expression did not differ significantly. Determination of the K-ras point mutations by automated TaqMan PCR in NSCLC tumour specimens is feasable and highly specific. Due to its high throughput capacity this method represents a valuable tool for routine screening.
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PMID:Automated real-time PCR to determine K-ras codon 12 mutations in non-small cell lung cancer: comparison with immunohistochemistry and clinico-pathological features. 1296 94


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