Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated. Correlations between these assays and some clinical and biological parameters were also studied. The repeatability and reproducibility of standard curves for the two methods gave a coefficient of variation (CV) of less than 4% and about 10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was examined by using dilution and recovery tests throughout the standard curves. The linear relations between theoretical and measured values, for these tests, had slopes close to 1 and an intercept near 0. The median value for EGF-R, measured on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein, the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median value, measured using the same population, was 2.75 human neu unit/micrograms protein, the mean value was 7.85 (range 1 to 125). There was an inverse relationship between EGF-R values and those for the estrogen receptor (ER), progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2 oncoprotein concentrations were positively correlated with ER, pS2 protein and cathepsin D. Furthermore, a significant positive correlation was observed between EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable. The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast cancer.
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PMID:[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters]. 888 58

The administration of neoadjuvant chemotherapy to breast cancer (BC) patients with operable disease allowed studies aimed of exploring the interaction between cytotoxic treatment and tumour biology in vivo. 99 patients with T2-4, NO-1, M0 primary BC received a median of 3 cycles of either CMF regimen (cyclophosphamide, methotrexate, 5-fluorouracil) or single agent epirubicin. Endocrine therapy was also concomitantly administered in the first 45 patients with estrogen receptor positive (ER+) BC. 92 ended the treatment plan. Ki67 labelling index, estrogen receptor (ER), progesterone receptor (PgR), and c-erbB-2 oncoprotein expression were evaluated immunohistochemically in tumour biopsies obtained before and after chemotherapy. At post-chemotherapy evaluation, tumour shrinkage greater than 50% was obtained in 71 patients (79.7%), 27 of them being complete responders (30.3%). The median Ki67 labelling index, which was 13% in the first biopsy, decreased to 4.5% (p < 0.001) upon mastectomy. No significant differences were observed in steroid hormone receptor and c-erbB-2 expression before and after neoadjuvant treatment. In conclusion, neoadjuvant chemotherapy, whether associated or not to endocrine therapy, leads to a significant decrease in BC proliferation without any appreciable impact on c-erbB-2 and steroid hormone receptor expression.
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PMID:Effect of neoadjuvant chemotherapy on Ki67 labelling index, c-erbB-2 expression and steroid hormone receptor status in human breast tumours. 892 Jul 76

One hundred and sixty-three breast carcinomas occurring in women aged between 26 and 44 years were examined for pathological features, oestrogen and progesterone receptor status, proliferation as determined by Ki-67 labelling and the presence of c-erbB-2 and p53 protein, and were compared with a control group of carcinomas from women in the 50-67 years age group. Carcinomas occurring in women aged under 35 years had a significantly high incidence of being poorly differentiated and of having high proliferation rates. This group also had a significantly high incidence of p53 protein staining. Carcinomas in the under 30 years age group had a lower incidence of oestrogen and progesterone receptor positivity. No differences were found in c-erbB-2-positive staining between the groups. Infiltrating lobular carcinomas were only identified in women aged 40 years and over. There was a higher incidence of a family history in the 35-44 years age group (18%) than in the under 35 years age group (11%). Breast carcinomas occurring in women aged under 35 years are more aggressive. An important finding is the high incidence of p53 positivity, which may indicate genetic instability.
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PMID:Breast carcinomas occurring in young women (< 35 years) are different. 895 95

The overexpression of two members of the erbB oncogene family-the epidermal growth factor receptor protein (EGF-R) and the HER-2/neu protein-in breast cancer has been investigated by numerous authors. Their exact role in breast cancer is still not defined. The simultaneous investigation of EGF-R and HER-2/neu in the same study population has only rarely been performed in breast cancer. Therefore, we analyzed the EGF-R and the HER-2/neu protein expression in 142 breast cancer specimens and 12 benign breast samples by immunohistochemistry. Results of the different expression analyses were compared with established clinicopathological parameters including estrogen and progesterone receptor status. In our study group EGF-R expression correlated with advanced tumor stage, axillary lymph node status and histological grade. HER-2/neu expression correlated with larger tumor size. Neither the evaluation of a single parameter of the erbB family nor the combination of both parameters showed a significant correlation with the disease-free and the overall survival of the individual patient with breast cancer. Only the expression of the progesterone receptor correlated with a better overall survival. Steroid hormone receptor expression and the expression of EGF-R and HER-2/ neu seem to be two independent phenomena in our samples of breast cancer. The simultaneous evaluation of EGF-R and HER-2/neu expression did not lead to new information of prognostic relevance.
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PMID:Expression analyses of epidermal growth factor receptor and HER-2/neu: no advantage of prediction of recurrence or survival in breast cancer patients. 896 Jan 38

Large core biopsy is a recently introduced method for pre-operative evaluation of breast lumps. The aim of this study was to evaluate the usefulness of this technique in providing pre-operative diagnostic and prognostic information that can lead to a correct line of treatment. We compared 41 cases of breast carcinomas diagnosed both by core biopsies and surgically removed samples. A high (93%) diagnostic agreement was obtained. Moreover, we found a significant correlation for mitotic count (r = 0.76), oestrogen receptor (r = 0.78), progesterone receptor (r = 0.80), p53 (r = 0.86) and c-erbB-2 (r = 0.90) analysis between core biopsy and definitive surgical pathology. An agreement for histological grading evaluation between the two techniques was obtained in 32 out of 40 cases (k = 0.65) whereas in the other cases, a lower grade was assigned by evaluating core biopsies. These findings suggest that percutaneous core breast biopsy is a valid tool for pre-operative management of breast lesions, but this should be confirmed in larger, prospective studies.
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PMID:Large core biopsy for diagnostic and prognostic evaluation of invasive breast carcinomas. 898 76

This retrospective case control study investigated the therametric value of the circulating c-erbB-2 gene product (Her-2, NEU) as (1) an eligibility criterion for high doses of chemotherapy and (2) response to standard adjuvant chemotherapy in node-positive breast cancer patients. Preoperative c-erbB-2 levels were measured in 211 locally advanced (> 3 nodes positive), pre- and perimenopausal breast cancer patients to determine if circulating levels of the gene product can assist in the determination of appropriate therapeutic options. 152 of 211 breast cancer patients received post-operatively a combination chemotherapy including the anthracycline analog mitoxantrone, while 59 patients were treated with conventional CMF therapy. Using 120 fmol/ml as a cut-off level, elevated c-erbB-2 values were found in 26 (12.3%) patients with locally advanced breast cancer. In univariate analysis significant survival differences were detected when c-erbB-2 'positive' patients were compared with c-erbB-2 'negative' patients. However, no significant survival differences were detected, when c-erbB-2 'positive' patients were compared according to regimen of adjuvant treatment. In multivariate analysis c-erbB-2 was an independent prognostic factor for predicting disease-free survival, but not for overall survival. High levels of c-erbB-2 were associated with low estrogen and progesterone receptor concentrations of the tumor cytosol. There was no correlation between elevated c-erbB-2 values and age, tumor size or degree of nodal involvement. c-erbB-2 was a better predictor of risk of recurrence than extent of nodal involvement or hormone receptor status.
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PMID:Influence of circulating c-erbB-2 serum protein on response to adjuvant chemotherapy in node-positive breast cancer patients. 906 2

Evidence is accumulating for a facilitative role for estrogen in ovarian cancer. Although response to antiestrogen therapy has been poor, there is a distinct subset of patients that respond. Strategies for treatment of ovarian cancer would be improved by identification of patients likely to respond to hormonal therapy. Cell culture models that are responsive or resistant to estrogen and antiestrogen may be of value in finding markers that predict responsiveness to hormonal therapy. Several model cell lines have been generated that express ER and proliferate in response to estrogen in vitro. Further studies are needed to better characterize the response of these ER positive cells lines to estrogen in vivo in mouse xenograft models. Expression of many of the same genes are regulated by estrogen in breast and in ovarian cancer cell lines. One exception may be the HER-2/neu oncogene product, which is down-regulated by estrogen in responsive breast carcinoma cells but not in two ovarian carcinoma cell lines. Initial analyses of several estrogen responsive and one resistant cell model suggests the potential value of progesterone receptor presence and low levels of HER-2/neu expression for predicting responsiveness to hormonal therapy. Additional cell models need to be investigated to determine the frequency with which these markers are associated with antiestrogen resistance.
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PMID:Estrogen action in human ovarian cancer. 913 8

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 controls, 112 patients with benign diseases and 534 patients with malignancies. Using 15 U/ml as the cutoff, no healthy subjects, patients with benign diseases (excluding liver cirrhosis) or patients with no evidence of disease (45 patients) had serum levels higher than this limit. Abnormal c-erbB-2 levels were found in 38.5% (10 of 26) of the patients with liver cirrhosis and in 26.7% (8 of 30) of those patients with primary liver cancer. No differences were found between the c-erbB-2 serum concentrations in liver cirrhosis or primary liver cancer, suggesting the possible catabolism of this antigen in the liver. Abnormal levels of this antigen were found in 20% (56 of 278) of the patients with breast carcinoma (locoregional 7%, metastases 41.5%), in 21% (6 of 28) of ovarian carcinomas (stage I-II 0%, stage III-IV 42.8%), in 21% (3 of 14) of the colorectal tumors (locoregional 0%, metastases 30%), and in 13.3% (11 of 83) of the patients with lung cancer (locoregional 11.5%, metastases 16%). C-erbB-2 sensitivity in other patients with advanced disease was: 25% (9 of 36) in prostatic cancer, 22% (2 of 9) in gastric cancer, and 11% (1 of 9) in vesical tumors. When patients with liver metastases were excluded abnormal c-erbB-2 serum levels were only found in breast, lung, prostatic and ovarian carcinomas. C-erbB-2 sensitivity in patients with lung cancer was related to tumor histology with significantly higher value in non-small cell lung cancer (mainly adenocarcinomas) than in patients with small cell lung cancer (p < 0.013). C-erbB-2 concentrations in patients with breast cancer were significantly higher in patients with recurrence (mainly bone and liver metastases) and in patients with progesterone receptor-negative (< 15 fmol/mg) tumors (p < 0.01). In conclusion, c-erbB-2 is not a specific tumor marker and abnormal serum levels may be found in patients with liver pathologies. Its sensitivity suggests its possible application as a tumor marker in breast, ovarian, lung (mainly adenocarcinomas) and prostatic tumors.
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PMID:Serum levels of C-erbB-2 (HER-2/neu) in patients with malignant and non-malignant diseases. 914 15

BRCA1 mutations, although implicated in disease predisposition in a major part of the hereditary breast cancer population, do not seem to be crucially involved in tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in genetic and biological features, as well as in clinical behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison group of stage II breast cancers were studied with regard to histopathological features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often DNA non-diploid, as well as being characterised by higher S-phase fraction values. These results suggest that BRCA1-induced breast cancers may manifest distinct tumour biological features of clinical importance.
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PMID:Tumour biological features of BRCA1-induced breast and ovarian cancer. 915 18

We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.
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PMID:Tissue expression and serum levels of HER-2/neu in patients with breast cancer. 939 44


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