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)

Epidermal growth factor receptor (EGFr) levels were analyzed in 140 primary breast cancer specimens by immunohistochemical assay (ICA), competitive binding assay (BA), or enzyme immunoassay (EIA). Thirty-nine of 118 specimens (33.1%) were scored as positive by ICA, 30 of 116 (25.9%; cut-off level 10 fmol/mg protein) by BA, and 31 of 80 (38.9%: cut-off level 5 fmol/mg protein) by EIA. Agreement on EGFr status was 72.3% (68/94) between ICA and BA, 77.0% (57/74) between BA and EIA, and 73.8% (59/80) between EIA and ICA. These discrepancies are based on assay differences and the heterogeneous distribution of cancer cells within specimens. Regardless of the assay method used, EGFr status had a significantly negative correlation with estrogen receptor status. Although EGFr-ICA and BA status had no relationship with prognosis, patients with medium and high EGFr-EIA level tumors (over 5 fmol/mg protein) had shorter relapse-free periods than those with low level tumors. However, the prognostic value of positive EGFr-EIA status was weaker than that of c-erbB-2 overexpression.
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PMID:Clinical value of enzyme immunoassay of epidermal growth factor receptor in human breast cancer. 791 60

Abnormal expression of p53, transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), and c-erbB-2 occurs in a variety of cancers and in some cases is associated with poor prognosis. Immunoperoxidase staining using these markers in formalin-fixed, paraffin-embedded endometrial carcinoma tissue was performed to determine whether immunoreactivity correlates with survival and known prognostic variables. Cases included 84 endometrioid adenocarcinomas, five adenoacanthomas, 12 adenosquamous carcinomas, 11 serous carcinomas, 15 clear cell carcinomas, and one carcinosarcoma for a total of 128 cases. Frequencies of immunoreactivity were as follows: p53, 37 of 128 (29%); TGF alpha, strong (2+) 23 of 128 (18%) and intermediate (1+) 26 of 128 (20%); EGFR, strong (3+) 21 of 128 (16%) and intermediate (2+ or 1+) 83 of 128 (65%); and c-erbB-2, strong (2+) four of 128 (2%) and intermediate (1+) three of 128 (1%). p53 and TGF alpha staining showed statistically significant correlations with decreased length of survival (P < .0017 and P < .0013, respectively, generalized Savage [Mantel Cox]). p53 immunoreactivity correlated with tumor types, grade, and stage. Transforming growth factor alpha staining correlated with increased depth of invasion and presence of vascular invasion. Epidermal growth factor receptor staining did not correlate with length of survival or known prognostic variables. c-erbB-2 staining correlated with tumor type. In the multivariate analysis p53 and TGF alpha staining were not independent predictors of survival when other variables were taken into account, including grade, stage, tumor type, presence of vascular invasion, and depth of invasion. Grade and stage were the only independent predictors of survival when used in combination in a Cox proportional hazards model.
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PMID:Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival. 792 13

Epidermal growth factor receptor (EGFR) overexpression correlates with both loss of estrogen receptor (ER) and poor prognosis in breast cancer. Interestingly, in normal breast EGFR appears to be expressed more frequently than in malignant tissue, and there may be a different relationship between ER and EGFR. A variety of cellular regulators, such as EGF, TGF alpha, phorbol esters, and steroid hormones, are capable of altering the level of EGFR expression in breast cells. However, much work remains to be done on the mechanistic details of EGFR regulation in this disease. The significance of EGFR as an oncogene in breast cancer is compounded by its potential interactions with other oncogenes such as c-erbB-2 and c-myc. Additionally, several recent studies have placed EGFR prominently in the signal transduction pathway, demonstrating that the EGFR-ligand system may play important roles throughout the course of malignant progression in breast cancer.
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PMID:EGF receptor expression, regulation, and function in breast cancer. 801 62

Epidermal growth factor receptor (EGFR) expression by human breast cancer has been shown to predict poor patient outcome, as has amplification of the c-erbB-2 proto-oncogene. We have developed a quantitative immunohistochemical method for measuring protein levels of both receptors and have applied this to a series of 123 breast primaries. We find EGFR expression is substantially lower than normal in nearly all breast cancers (97%). Quantification of p185erbB-2 indicates overexpression in 91% of the tumors. Two separate tumor populations are apparent with levels of c-erbB-2 expression ranging from 0.33 to 19 and 45 to 480 times normal, respectively. Within the lower population, p185erbB-2 expression is inversely related to EGFR expression (rank correlation, P < 0.0005). Using fluorescent in situ hybridization we show that tumors in the latter population have c-erbB-2 amplification and that amplification is restricted to this group. Our findings indicate that significant overexpression of p185erbB-2 occurs in the absence of amplification; these lower levels of expression may have functional significance. Fifty-three patients underwent in vivo bromodeoxyuridine labeling, allowing flow cytometric analysis of tumor cell cycle kinetics. EGFR expression correlates directly to the labeling index (P = 0.011) and indirectly to potential doubling time (P = 0.010), but not to the duration of the S-phase (P = 0.502). Conversely, p185erbB-2 expression does not relate to indices of proliferation. Our results have important implications for the use of both receptor types as therapeutic targets.
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PMID:Quantitative estimation of epidermal growth factor receptor and c-erbB-2 in human breast cancer. 870 30

Epidermal growth factor receptor (EGF-R) and the oncogene product of c-erbB-2 have been shown to be expressed in human tumors and in some cases relate to clinical outcome. This study investigates the correlation between the presence of these receptor proteins and various histological grades of cervical tissues. Immunocytochemical analysis of benign, premalignant and malignant cervical tissues showed a highly significant correlation between the expression of the two proteins and the histological grade of the lesions. Moreover, the overall frequency of coexpression of these proteins was similar. This study suggests that these proteins may be involved in cellular proliferation and have a significant role in the progression of cervical cancer.
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PMID:c-erbB-2 oncoprotein and epidermal growth factor receptor in cervical lesions. 930 83

We measured neovascularization, epidermal growth factor receptor, and c-erbB-2 expression in a consecutive series of 233 surgically resected axillary lymph node-negative breast cancer patients with a long-term follow-up to define the usefulness of these parameters as independent prognostic indicators of overall survival (OAS). Microvessel count (MVC), as a measure of neovascularization, was determined using a monoclonal antibody against human factor VIII-related antigen. The median MVC of 20 (range, 4-76) was used as a cutoff value for discriminating between low and high vascularized tumors. Epidermal growth factor receptor and c-erbB-2 expression were evaluated by immunohistochemistry. Tumors were considered positive if >10% of the cells showed specific membrane staining. OAS curves were estimated by the Kaplan-Meier method. The independent prognostic effect of each variable was determined with the Cox proportional hazards model. High MVC (P = 0.04), high nuclear grade (P = 0.005), and high S-phase (P = 0.02) significantly affected OAS at univariate analysis. In a Cox multivariate analysis, the characteristics with an independent prognostic effect on OAS were: MVC (relative hazard, 2.12; 95% confidence interval, 1.18-3.81; P = 0.01) and nuclear grade (relative hazard, 2.83; 95% confidence interval, 1.12-7.17; P = 0.01). These results demonstrate that quantification of neovascularization adds useful independent prognostic information on survival in node-negative breast cancer patients with long-term follow-up.
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PMID:Measurement of neovascularization is an independent prognosticator of survival in node-negative breast cancer patients with long-term follow-up. 1053 53

Activation of the ras oncogene is an important step in carcinogenesis. Human MCF-10A mammary epithelial cells were transformed with a point-mutated form of the Ha-ras oncogene. Epidermal growth factor receptor (EGFR) phosphorylation levels were chronically elevated after EGF induction and the EGFR ligand-driven internalization rate was slower in Ha-ras transformed MCF-10A cells. Additionally, basal levels of p42/44 mitogen-activated protein kinase (MAPK) expression and enzyme activity were significantly higher in Ha-ras transformed cells, localized predominantly in the nucleus. The anti-EGFR monoclonal antibody (MAb) 225 and the EGFR tyrosine kinase inhibitor PD153035 blocked anchorage-independent growth of Ha-ras transformed cells in soft agar and were more effective when used in combination. The MEK inhibitor PD98059 and anti-erbB-2 MAb L26 also suppressed colony formation of Ha-ras transformed cells in soft agar. Therefore, Ha-ras transformation leads to an augmentation in signaling through the EGFR as a result of an increase in ligand-dependent phosphorylation, a decrease in its internalization and an up-regulation in basal p44/42 MAPK levels. These effects may contribute to uncontrolled growth of Ha-ras-transformed human mammary epithelial cells.
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PMID:RAS transformation causes sustained activation of epidermal growth factor receptor and elevation of mitogen-activated protein kinase in human mammary epithelial cells. 1096 38

Epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor-alpha (TGF-alpha), play an important role through the autocrine growth-regulation system in several human cancers, including breast cancer. However, the clinical significance of co-expression of EGF-R and TGF-alpha has not been elucidated. One hundred seventy-three female patients diagnosed as invasive ductal carcinoma who had undergone a mastectomy (159 patients) or breast-conserving surgery (14 patients) were followed up for 81 to 119 months (median 94 months) post-operatively. Immunoreactivity for EGF-R, TGF-alpha, p53 and c-erbB-2 with paraffin-embedded carcinoma tissue was investigated using labeled streptavidin-biotin methods. Positive rates of carcinoma cells were 27%, 33%, 32% and 26% for EGF-R, TGF-alpha, p53 and c-erbB-2, respectively. Expression of EGF-R only was observed in 16% (28/173), of TGF-alpha only in 22% (38/173), of both EGF-R and TGF-alpha in 11% (19/173) and of neither in 51% (88/173). By univariate analysis, significant differences in overall survival and disease-free survival were noted according to the co-expression of EGF-R and TGF-alpha (p< 0.0001, p<0.0001), co-expression of EGF-R and c-erbB-2 (p = 0.0029, p = 0.0028), nodal status (p = 0.0028, p = 0.0001), tumor size (p = 0.0001, p<0.0001) and c-erbB-2 expression (p = 0.0034, p = 0.018), respectively. The status of p53 expression (p = 0.01), estrogen receptor (p = 0.042) and progesterone receptor (p = 0.046) showed significant differences in overall survival. According to Cox's multivariate analysis, co-expression of EGF-R and TGF-alpha had the most significant effect on disease-free survival (p<0.0001) and overall survival (p<0.0001), followed by nodal status. Co-expression of EGF-R and TGF-alpha by immunohistochemical detection is an independent prognostic indicator, and it may be helpful for determining the group of breast-cancer patients with an aggressive phenotype.
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PMID:Co-expression of epidermal growth factor receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer patients. 1110 91

Epidermal growth factor receptor 1 (EGFR-1) overexpression is usually described as linked with a worse prognosis in a variety of tumours of epithelial origin. However, its role in ovarian cancer is still controversial. The aim of the present study was to analyse the prognostic impact of EGFR-1 in a retrospective series of 93 stage III-IV primary ovarian epithelial tumours. All patients, enrolled in a multicentre GINECO prospective clinical trial, were treated with the same platinum-based combination chemotherapy, and were followed up with a median of 69 months. Epidermal growth factor receptor 1 plasma membrane expression, assessed by immunohistochemistry on paraffin-embedded tissues, was correlated with clinical parameters as well as immunohistochemical expression results of HER-2 (c-erbB-2), BAX, BCL-2, p53 and anti-Ki-67, previously studied in the same series of patients. Positive immunostaining for EGFR-1 was seen in 31 of the 93 analysed cases (33%). No correlation was found between EGFR-1 expression and clinical parameters. No correlation was found between EGFR-1 expression and other biological markers, except for HER-2, which was limit for significance. Indeed, among the EGFR-1-negative cases, 10.3% expressed HER-2, whereas the HER-2-expressing tumours accounted for 27.6% of EGFR-1-positive cases (P=0.06). Epidermal growth factor receptor 1 overexpression had no prognostic impact on both overall and progression-free survival through univariate and multivariate analyses. The potential effect of EGFR-1 and HER-2 co-expression on targeted therapy against EGFR-1 and/or HER-2 molecules has to be further analysed.
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PMID:Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group). 1522 74

HER2 overexpression has been associated with anti-estrogen resistance in human breast cancer, and it has been suggested that the combined treatment of an anti-HER2 antibody plus tamoxifen has enhanced anti-cancer efficacy in breast cancer. The detailed anti-proliferative interactions between trastuzumab and tamoxifen were analyzed with the isobologram and Chou and Talalay methods, which assess the presence of synergy, addition or antagonism. We used the breast cancer cell lines that are estrogen receptor (ER)-positive and HER2-positive. We also analyzed the molecular changes on the HER2 and (ER) signaling pathways that are induced by trastuzumab plus tamoxifen. In terms of cancer cell proliferation, the simultaneous combination of trastuzumab and tamoxifen on BT-474 cells was more growth inhibitory (44%) than the treatment with trastuzumab (24%) or tamoxifen (31%) alone. Isobologram analysis of simultaneous trastuzumab plus tamoxifen exposure showed, however, that there were antagonistic interactions at an effect level of 30% (IC30). Using Chou and Talalay analysis we also observed antagonistic interactions at lower levels of cell kill, although there were additive effects at highest levels of cell kill. Trastuzumab followed by tamoxifen showed antagonism at all effects levels. Tamoxifen followed by trastuzumab showed antagonism at lower levels of cell kill, and additivity at higher levels of cell kill. Similar interactions were observed using T47D cells. The molecular effects of the combined treatment with trastuzumab plus tamoxifen on the levels of HER2 and ER signaling showed that, with respect to HER2 protein levels, trastuzumab downregulated HER2 by 27%, tamoxifen upregulated HER2 by 40%, and the combination of trastuzumab plus tamoxifen did not induce changes in HER2 respect to control. With respect to HER2 mRNA, trastuzumab upregulated HER2 mRNA to 367%, tamoxifen to 166%, and the combination to 401%. With respect to HER2 phosphorylation, trastuzumab upregulated HER2 phosphorylation to 352%, tamoxifen to 202% and the combination to 633%. Epidermal growth factor receptor levels were not changed by trastuzumab or tamoxifen alone, and were upregulated to 138% by the combination. The protein levels and activity of extracellular recptor kinase were not modified by trastuzumab, tamoxifen or the combination. Finally, estrogen receptor protein and mRNA levels were downregulated to about 50% by trastuzumab, tamoxifen or the combination. Taken together, our results show that in ER-positive breast cancer cells overexpressing HER2, trastuzumab plus tamoxifen have antagonistic interactions when used in combination, and that this antagonism may be related with an increase in HER2 signaling pathways that occurs when tamoxifen is added to trastuzumab.
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PMID:Trastuzumab plus tamoxifen: anti-proliferative and molecular interactions in breast carcinoma. 1531 65


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