Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perturbations of oncogenes in breast carcinoma include amplifications of the HER-2/neu and PRAD1 genes, as well as p53 mutations. Some of these lesions frequently appear in early cancers such as ductal carcinoma in situ and are stable as the tumors become invasive and metastasize. Thus these findings suggest that oncogene mutations may define a point of origin for a given breast cancer, and are fixed lesions during tumor progression. Such germline abnormalities may occur at the BRCA1, H-RAS VNTR, and p53 loci. The rational use of genetics may be to identify women at high risk for the development of breast cancer so that they may be enrolled in future chemoprevention trials.
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PMID:Oncogenes, breast cancer, and chemoprevention. 800 94

Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.
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PMID:Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients. 809 50

The c-erbB-2 protein was measured in sera of patients with breast cancer or benign breast diseases to study the significance of this protein as a tumor marker. The mean value and positive rate for this protein (assuming 20U/ml as the cut-off value) were 11.8 U/ml (0%) in benign breast disease (n = 30), 11.8 U/ml (3.1%) in stage I/II primary breast cancer (n = 64), 38.2 U/ml (29.4%) in stage III/IV primary breast cancer (n = 17), 17.9 U/ml (33.3%) in locally recurrent breast cancer (n = 12), 298.4 U/ml (51.0%) in recurrent breast cancer with distant metastases (n = 51), and 12.9 U/ml (0%) in those with no evidence of recurrence (n = 57). Thus, the serum c-erbB-2 protein level was significantly higher in the distant metastatic group. In patients with distant metastases, there was a close association between expression of c-erbB-2 protein in the primary tumor and the serum c-erbB-2 protein level. On the basis of these results, serum c-erbB-2 protein was thought to be useful as a tumor marker for postoperative monitoring of breast cancer, especially in patients positive for expression of this protein in primary cancer tissue.
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PMID:C-erbB-2 protein in the sera of breast cancer patients. 809 69

Lymph node status is still the single most important prognostic factor in breast cancer. Axillary surgery remains the only reliable means of providing this information. This pilot study evaluates using a highly specific radiolabelled monoclonal antibody to provide equivalent information by a non-invasive technique. After optimisation of labelling conditions, our first antibody, ICR12 (against the gene product of c-erbB-2) was evaluated in a mouse model system. Twenty-four hours post i.v. injection the mice were killed and their organs, blood and tumours harvested for counting. Tumour localisation was four times greater than that into normal tissues, reaching 20% injected dose per gram of tumour. Eight patients have had this Tc99m-ICR12. Patient selection was by immunocytochemical staining of fine needle aspirates from the patient's own breast cancer. After intravenous administration of the immunoconjugate, tomographic images were obtained at 24 h. These results were compared to the subsequent histopathological examinations. Three patients acted as normal controls, one patient was negative due to inappropriate sampling, and two patients had strong membrane staining and provided excellent tumour localisation to both breast primary and regional node metastases. A further two patients only had moderate antigen expression on staining and did not localise well. The good performance of this radiolabelled antibody with patients that strongly stain for the antigen encourages the development of this system as both a method of staging breast cancer and a potential means of immunotherapy in this subgroup of patients.
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PMID:Radioimmunolocalisation in breast cancer using the gene product of c-erbB2 as the target antigen. 809 4

One-hundred and sixty-four patients with gastric carcinomas, who underwent gastrectomy during 1979-1985, were studied. Sixty-five of these cases were early gastric carcinomas, and the others were advanced gastric carcinomas, and the others were advanced gastric carcinomas. The nuclear DNA contents were measured by cytofluorometry, and immunohistochemical study on the expression of c-erbB-2 protein was performed using a monoclonal antibody against the c-erbB-2 oncogene product. Furthermore, immunohistochemical detection of proliferating cell nuclear antigen (PCNA) was performed using a monoclonal antibody against the PCNA. The rates of positive invasion beyond submucosal layer, lymphatic invasion, and vascular invasion in aneuploid cases were significantly higher than those in diploid ones, and the patients with aneuploid tumor had a significantly worse prognosis than those with diploid tumor. The rates of positive lymph node metastases and invasion beyond submucosal layer in the group with positive staining of the c-erbB-2 protein was significantly higher than in the negative group, and the group with positive staining for c-erbB-2 had a significantly worse prognosis than the negative one. PCNA indices showed a significant correlation with lymph node metastasis, and the group with higher PCNA indices had a worse prognosis. The patients with tumor showing both aneuploid and positive staining for c-erbB-2 protein, had the worst prognosis. There is a relationship between c-erbB-2 tissue status and PCNA indices, but no correlations were found among c-erbB-2 tissue status, PCNA indices and DNA contents. From these results, it can be concluded that DNA ploidy, c-erbB-2 protein, and PCNA may reflect the malignant potential of gastric carcinoma.
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PMID:[Correlation of DNA ploidy, c-erbB-2 protein tissue status, level of PCNA expression and clinical outcome in gastric carcinomas]. 809 98

The immunodetection of HER-2/neu oncogene product was performed in 108 breast carcinomas using immunoperoxidase technique. Monoclonal anti HER-2/neu protein was applied on frozen sections. Immunoprecipitates were evaluated by a computerized system of image analysis (SAMBA). The percentage of the immunostained tissue surfaces and mean optical densities were correlated with the 5 year overall and disease-free survival rates. It was shown that in optimal conditions of antigen preservation and standardized method of immunoprecipitates evaluation, 67% of breast carcinomas were more than 20% pHER-2/neu positive. The pHER-2/neu overexpression was not significantly correlated with the overall 5 year survival. However large positive anti pHER-2/neu surfaces were correlated with higher risk of recurrence (p = 0.0013) and of metastases (p = 0.035).
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PMID:Immunodetection of HER-2/neu protein in frozen sections evaluated by image analysis: correlation with overall and disease-free survival in breast carcinomas. 810 Apr 12

Amphiregulin is a recently described member of the epidermal growth factor family. Primary breast cancers were assessed for expression of amphiregulin by immunochemistry (111 cases), Northern, and/or dot blots (68 cases). Epidermal growth factor and estrogen receptors were measured in all cases. p53 and erbB-2 expression was assessed by immunohistochemistry for most cases. There was no association of these factors with amphiregulin expression, which was detected by immunochemistry in 40 of 111 cases. A significant association of amphiregulin expression assessed by Northern dot blots versus immunochemical staining was seen (P = 0.0016). Expression was not detected in adjacent nontumor tissue by immunochemistry. Amphiregulin was expressed in tumor epithelium, but not stromal or inflammatory cells. Expression was more common in lymph node positive cases (23 of 49; 47%) than lymph node negative cases (11 of 42; 26%; P = 0.04). The coexpression of epidermal growth factor receptor and amphiregulin in 35% of epidermal growth factor receptor positive cases raises the possibility of an autocrine loop in this subset of patients. Amphiregulin stimulates fibroblast growth and is up-regulated in breast cancer. A possible effect on tumor stroma may relate to the association with metastases.
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PMID:Amphiregulin, epidermal growth factor receptor, and estrogen receptor expression in human primary breast cancer. 810 63

We investigated the prognostic significance of Helix pomatia lectin (HPA) staining on disease-free and overall survival in 120 primary breast carcinomas. HPA staining was present in 58 (48%) of these carcinomas. It was significantly associated with axillary lymph node metastases (P < 0.001) and c-erbB-2 expression (P < 0.01). A univariate study revealed that disease-free and overall survival were significantly correlated with clinical stage, tumour size, axillary lymph node metastases. HPA staining and c-erbB-2 expression. In a multivariate study, all previous prognostic indicators except HPA staining and c-erbB-2 expression were independent factors. However, stratifying the patients on the basis of HPA and c-erbB-2 status suggested that HPA +/c-erbB-2+ status was predictive of a higher incidence of axillary lymph node metastases (P = 0.000001) and a poorer overall (P < 0.0002) and a shorter disease-free (P < 0.000006) survival when compared with the other subgroups, although this combination did not provide any additional prognostic information for overall (P = 0.3544) or disease-free (P = 0.7152) survival by a multivariate analysis. For patients in whom axillary lymph node dissection has not been performed, therefore, HPA and c-erbB-2 status seems to be a powerful tool to discriminate subpopulations with a high recurrence risk and shorter survival who should undergo more aggressive therapy.
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PMID:Prognostic significance of Helix pomatia lectin and c-erbB-2 oncoprotein in human breast cancer. 810 37

This study was conducted to see whether the accuracy in predicting liver metastases in gastric cancer patients increased when DNA aneuploidy and c-erbB-2 gene products were analyzed besides other clinicopathologic features. Aneuploidy was observed in 32 out of 74 tumors (43%); these included 62% of those tumors in patients with liver metastases, 43% of those with peritoneal dissemination and 26% of those in the 5-year survival group. Aneuploidy was positively correlated with the prognosis and degree of blood vessel invasion but not with lymph node metastases or lymphatic permeation. Positive staining for the c-erbB-2 gene product was detected in 19 out of 89 tumors (21%). This staining was not related to any of the clinicopathologic features examined. Multivariate analysis revealed that the degree of blood vessel invasion was the factor that most strongly correlated with liver metastases. The prognostic value of aneuploidy was significant (p < 0.05) but much smaller than that of blood vessel invasion (p < 0.0001), interstitial tissue reaction (p = 0.02), Borrmann type classification (p = 0.03). Analyses of DNA aneuploidy and c-erbB-2 gene expression in the primary tumor of gastric carcinoma to improve the accuracy of predicting liver metastasis seem to be of limited clinical value at present.
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PMID:Predictive value of c-erbB-2 and DNA ploidy patterns in gastric carcinoma recurrence. 810 19

If axillary lymph node metastases were able to be accurately predicted, dissection could be avoided in some patients with breast cancer whose axillary nodes are clinically negative. In this study, we assessed the relationships between histological axillary lymph node metastases and clinical axillary nodal status, tumor size, DNA-ploidy, c-erbB-2 expression, and the score of the argyrophilic nucleolar organizer region. We then attempted to evaluate their predictive values for axillary lymph node metastasis in 173 patients with invasive breast cancer, retrospectively. The clinical and biological variables were significantly correlated with the presence and degree of axillary lymph node metastases. A metastatic index, calculated from the clinical and biological variables, proved especially useful for predicting axillary lymph node metastases in patients whose axillary nodes were clinically negative. However, the predictive abilities were still limited and thus it was concluded that as yet, only axillary dissection can provide accurate information on axillary lymph node metastases.
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PMID:A retrospective study on the clinical and biological prediction of axillary lymph node metastasis in breast cancer. 810 89


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