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)

In the present study we update previous results on the prognostic value of intratumoral microvessel density (IMD), determined immunocytochemically using the monoclonal antibody CD-31 and a standard streptavidin-immunoperoxidase technique, published in the J Clin Oncol 12:454-466, 1994. This study was undertaken in those 211 node-negative breast cancer (NNBC) cases of that series of which we had pathological material available to determine all the prognostic indicators. The median period of follow-up has been extended to 78 and 80 months for relapse-free survival (RFS) and overall survival (OS), respectively, and new biological indicators (i.e. Ki-67 labeling and 67 kDa laminin receptor expression) were included in the analysis. The main results obtained are: i) a confirmation that IMD is not associated with the other biological markers studied, i.e. expression of p53 protein, c-erbB-2 protein, 67 kDa laminin receptor, and cell kinetics; IMD was weakly associated only with histological grade (p = 0.053); ii) IMD remains a highly significant prognostic factor for RFS and OS (p < 0.0001 and p = 0.018, respectively) in univariate analysis; iii) in multivariate analysis on RFS, IMD (likelihood ratio test (LRT) = 30.16; p < 0.0001), 67 kDa laminin receptor (LRT = 9.80; p = 0.0017), the IMD/67 kDa laminin receptor interaction (LRT = 8.62; p = 0.0033), tumor size (LRT = 8.56; p = 0.0034), and p53 protein (LRT = 4.96; p = 0.025) are significant and independent prognostic indicators. For OS, only tumor size (LRT = 8.34; p = 0.0038), menopausal status (LRT = 5.16; p = 0.023), p53 protein (LRT = 4.37; p = 0.036), and IMD (LRT = 4.05; p = 0.044) retain a significant and independent prognostic value. The results of this study confirm the prognostic importance on RFS of the variables previously tested, but not of peritumoral lymphatic vessel invasion. A novel finding is that 67 kDa laminin receptor and the IMD/67 kDa laminin receptor interaction are also significant and independent variables. For OS, the results confirm that both IMD and tumor size are significant and independent variables. With prolonged follow-up the novel finding that emerges is the prognostic importance of menopausal status and p53 protein. This new information could be useful for a more accurate selection of high-risk NNBC patients who require careful follow-up and may benefit from adjuvant therapy.
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PMID:Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma--results of a multiparametric study. 853 68

Uterine malignant mixed mesodermal tumors (MMMT) are highly malignant tumors containing both malignant glands and stroma, while adenosarcomas (AS) are less aggressive tumors composed of malignant stroma and benign glands. Immunohistochemistry was used to grade overexpression of p53 protein, HER-2/neu protein, epidermal growth factor receptor (EGFR), and Ki-67 antigen in both the glands and stroma of tissue from 20 women with MMMT and 6 women with AS. EGFR was overexpressed in 2 AS and 9 MMMT, and was more commonly found in the sarcomatous component than the carcinomatous component in MMMT (P = 0.03). p53 was not found in any AS samples and was strongly present in 6 MMMT samples with a random distribution between the malignant components. HER-2/neu protein was not overexpressed in any AS or primary MMMT. Ki-67 antigen, a marker of cell proliferation, was found at higher levels in MMMT than AS samples (P = 0.03) and high Ki-67 antigen expression correlated with a decreased survival in patients with MMMT (P = 0.004). Independent characterization of oncogene proteins in the malignant components of these heterogeneous tumors may provide insight into the histogenesis and behavior of these malignancies.
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PMID:The expression of epidermal growth factor receptor, HER-2/Neu, p53, and Ki-67 antigen in uterine malignant mixed mesodermal tumors and adenosarcoma. 855 33

Immunohistochemically detected metallothionein expression [MT(+)] was shown to be related to aggressive behavior of the invasive ductal carcinoma of the breast. In this study, MT expression was examined immunohistochemically in 92 cases of invasive breast carcinoma and compared with immunohistochemically demonstrated estrogen receptor (ER), c-erbB-2, Ki-67 status and clinicopathological characteristics. Of the 92 cases examined, 27.1% (25 cases) were MT(+), and high percentages of the solid tubular subtype of invasive ductal carcinoma (47%), medullary carcinoma (80%), and carcinomas with spindle cell metaplasia (100%) were positive for MT. MT(+) carcinomas showed tendency to have highly atypical nuclei, and nuclear staining for Ki-67 antigen was found in a higher percentage of cases than in MT(-) carcinomas. An inverse relationship between MT(+) and ER immunoreactivity was observed. MT expression was not associated with age distribution, menopausal status, tumor size or lymph node metastasis. The overall survival rate in MT(+) cases was worse than in those negative for MT, but no significant association was found. MT(+) was not associated with poor prognosis in total, estrogen receptor-negative or node-negative tumors. These findings suggest that MT expression in breast cancer cells is related to cell-proliferative activity, and that dedifferentiation of carcinoma cells may play a role in induction of MT expression.
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PMID:Immunohistochemical expression of metallothionein in invasive breast cancer in relation to proliferative activity, histology and prognosis. 860 36

The expression of epidermal growth factor receptor (EGFR), c-erbB-2, and c-erbB-3 was examined immunohistochemically in 57 cases of periampullary carcinoma. The percentage of Ki-67-positive cells was also examined in the same tissue, to determine the relationship between the expression of the members of the type I growth factor receptor family and cell proliferation. In carcinoma of the head of pancreas, the percentage of cases with overexpression of c-erbB-3 was significantly higher than with overexpression of c-erbB-2 and EGFR. In contrast, in lower bile duct carcinoma and carcinoma of the ampulla of Vater, the percentages of cases with overexpression of c-erbB-2 was greater than with overexpression of other growth factor receptors. A higher percentage of cases with overexpression of c-erbB-3 in pancreatic head carcinoma and overexpression of c-erbB-2 in carcinoma of the ampulla of Vater was found in Ki-67 antigen-positive cases. Moreover, the overexpression of c-erb-3 in pancreatic head carcinoma, c-erb-2 in ampulla of Vater carcinoma, and Ki-67 in both carcinomas was found to be associated with poor patient outcome. These results demonstrate that different members of the type I growth factor receptor family are overexpressed in different carcinomas of the periampullary region.
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PMID:Overexpression of different members of the type 1 growth factor receptor family and their association with cell proliferation in periampullary carcinoma. 868 79

Expression of the molecular biological factors (MBFs) c-erbB-2, Ki-67 antigen, and tenascin (TN) was assessed immunohistochemically in specimens from patients who had undergone surgery for carcinoma of the papilla of Vater. The MBFs were then analyzed by histological factors (v, d, panc, n, Stage), which have been demonstrated to be outcome predictors, and by patient outcome. None of the MBFs showed any significant correlation with the histological factors. There were significant differences (p < 0.05) in the expression of c-erbB-2, Ki-67 antigen, and TN between patients who survived >5 years and those who survived <5 years. The patients with greater expression of c-erbB-2, Ki-67 antigen, and TN had a poor prognosis, whereas those with less expression had a good prognosis. They were therefore considered independent predictors of outcome for carcinoma of the papilla of Vater. Combined analysis of both histological factors and MBFs was also performed, with the result that the combined analysis of MBFs yielded a better prediction of outcome in carcinoma of the papilla of Vater than analysis of either one histological factor or MBF.
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PMID:Combined analysis of expression of c-erbB-2, Ki-67 antigen, and tenascin provides a better prognostic indicator of carcinoma of the papilla of Vater. 872 Jun 69

Cancer chemoprevention is defined as intervention by chemical agents prior to invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint biomarkers in chemoprevention studies may reduce the size, length and cost of clinical prospective randomized trials in high-risk populations. Intermediate biomarkers are measurable alterations in the tissues at risk and include differentiation, genetic composition, biochemical expression, and proliferation. Assessment is possible because invasive epithelial neoplasms are known to begin as intraepithelial proliferations with a spectrum of cellular abnormalities extending to carcinoma in situ. Genetic heterogeneity begins in the intraepithelial phase; a stochastic accumulation of genetic errors characterizes the progression of clonal evolution within the tumor through the process of invasion and metastasis. Pathologic features associated with this process include tumor classification as well as whether it is intraepithelial or invasive. If the process is intraepithelial, the grade and extent of the intraepithelial lesion are reported. If the neoplasm is invasive, tumor size, extent, degree of differentiation (histologic and nuclear grade), mitotic rate, vascular invasion, and lymph node involvement are evaluated. In assessing biomarkers relevant chemoprevention, and without complete regression of the neoplasm with the chemopreventive agent or agents, measurable parameters along with histopathologic features are applicable. Three methods readily applicable for this purpose that can be applied to paraffin-embedded, formalin-fixed tissue include quantitative pathology, immunohistochemistry, and molecular biologic applications. These methods require some consistency in handling and processing the tissues under study; results may deteriorate due to a number of processing variables, including time to fixation, time in fixative, and fixative type. Quantitative pathology, including static image analysis and flow cytometry, can determine total DNA content. Using static image analysis, very small tumors can be studied. In addition, adjacent intraepithelial and invasive components of a tumor may be studied from a single slide. Steroid receptors, oncogenes, and other proteins detectable through immunohistochemical or molecular biologic methods can be quantitated by this technique as well. Cell cycle synthetic function is assayable by both methods. Flow cytometry can calculate the total percentage of cells in S-phase, or the tumor cell S-phase fraction based on the percentage of cells detected between the G0, G1 peak and the G2 + M peak. A similar approach is generally not applicable with current image analysis equipment; however, cell cycle related proteins such as MIB-1 (Ki-67 associated) can be quantified. Immunohistochemical methods can employ a wide variety of monoclonal antibodies to detect oncogene related proteins, including HER-2/neu (c-erbB-2) and p53. Molecular biologic methods, including in situ hybridization, polymerase chain reaction, and in situ PCR, can have many applications when applied to paraffin-embedded tissues, including detection of viral DNA, identification and measurement of apoptosis, and defining gene deletions.
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PMID:Role of the pathologist in biomarker studies. 874 73

The evaluation of the immunohistochemical expression of epidermal growth factor receptor (EGFR), c-erbB-2 oncoprotein, proliferating indices Ki-67, and PCNA were determined on 68 primary breast carcinomas. These markers were correlated with each other and with other clinicopathological variables such as: age, tumor size? histotype, tumor grade and steroid receptors' content as well as nodal status. The monoclonal antibodies anti-human Epidermal Growth Factor Receptor (EGFR1), anti-human Ki67 (DAKO) and N13259 (Oncogene Science) were applied to paraffin and frozen tissue sections. All markers showed an heterogeneous pattern of staining. There was almost equally high staining intensity at the membranus for EGFR and c-erbB-2 in about 32% of the cases. The EGFR and c-erbB-2 positive cases were much less common in infiltrating lobular (2,2/13) rather than in ductal adenocarcinomas (21,20/55). The low grade carcinomas showed low expression of EGFR and c-erbB-2 oncoprotehl comparing with high grade ductal adenocarcinomas. A high index of Ki-67 was correlated with EGFR and c-erbB-2 membrane positivity. There was an inverse relationship between the expression of c-erbB-2 and EGFR, when compared with oestrogen receptors' content. A significant correlation was also demonstrated between EGFR and c-erbB-2 immunoreactivity with lymph node status. Our results provide evidence that the synchronous immunohistochemical detection of EGFR, c-erbB-2 and Ki-67 may be of useful significance in breast cancer patients, especially when combined with other clinicopathological variables. Furthermore the expression of EGFR and c-erbB-2 oncoprotein may affect the cell proliferation and differentiation.
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PMID:The prognostic significance of epidermal growth factor receptor (EGFR), C-erbB-2, Ki-67 and PCNA expression in breast cancer. 892 Jul 82

The development and progression of cancer are known to be regulated by various oncogenes and tumour suppressor genes. We analysed 63 primary malignant salivary gland tumours for the expression of p53 and c-erbB-2 proteins. Immunohistochemically, 7 of 63 tumours (11%) showed diffuse nuclear staining for p53 protein, and all 7 were also positive for c-erbB-2 protein. The overexpression of p53 protein correlated closely with the overexpression of c-erbB-2 protein (P<0.001). Overexpression of both p53 and c-erbB-2 proteins (coexpression) was found in tumours of certain histological types, such as adenocarcinoma, carcinoma in pleomorphic adenoma, and salivary duct carcinoma. Furthermore, it is noteworthy that coexpression was associated with high-grade carcinoma, advanced tumour stage, and a high Ki-67 labelling index (%) which is a marker of cell proliferation. In adenocarcinoma, we attempted to clarify the relationship between coexpression and histological grade. Coexpression was associated with histological grades showing high mitotic indices and necrotic areas, which reflected high cell-proliferative activity. These results suggest that the accumulation of genetic alterations, such as those involving p53 and c-erbB-2, plays an important part in the progression of malignant salivary gland tumours.
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PMID:Coexpression of p53 and c-erbB-2 proteins is associated with histological type, tumour stage, and cell proliferation in malignant salivary gland tumours. 892 28

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 class I tyrosine kinase growth-factor receptors include epidermal growth factor receptor (EGFR), ErbB2 (c-erbB-2, HER-2/neu), ErbB3 and ErbB4. To elucidate their role in the regulation of homeostasis and carcinogenesis, we examined the expression of the receptors in normal urothelium and in urothelial carcinoma by immunohistochemistry. EGFR was expressed in the basal cells of normal urothelium, while ErbB2, ErbB3 and ErbB4 were present mainly in the superficial layer. A distinct reciprocal distribution was observed between the EGFR and the remaining members of the subclass (P = 0.0001). Both BCL-2 protein and Ki-67 antigen (MIB-1) showed a strong positive association with EGFR (P = 0.002) and an inverse correlation with ErbB2, ErbB3 or ErbB4 (P = 0.0004, 0.0000, and 0.001, respectively). With regard to carcinoma, there was no important relationship between receptor overexpression and tumour grading (P > 0.1), while only EGFR overexpression was correlated with muscular invasion (P = 0.02). Coexpression of EGFR-ErbB3 and ErbB3-ErbB4 was more often detected in high-grade tumours and correlated with the extent of tumour invasion. Our data indicate that class I receptors are differentially expressed in normal urothelium in vivo, but an orchestrated expression pattern does not exist during tumorigenesis.
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PMID:Expression patterns of erbB receptor family in normal urothelium and transitional cell carcinoma. An immunohistochemical study. 923 Sep 11


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