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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study is to evaluate the correlation of some established prognostic factors, hormone receptor and C-erbB-2 expression of breast cancer patients in Yogyakarta, Indonesia. Beginning January 1997, 60 breast cancer patients who were treated either by mastectomy, breast conserving surgery or biopsy, were evaluated clinically in connection with age, menopausal status, stage, tumor size, nodes; also histologically regarding type, grade and mitotic index. Patients were evaluated for estrogen and progesterone receptor, as well as C-erbB-2 expression with immunohistochemical techniques. Median age was 47.5 years old, range from 28 to 80 years old. Most of them were premenopause (65.0%). One patient (1.7%) was a man. Most of the patients were stage IIB (25.0%), 51.7% with positive estrogen receptor and 65.9% with positive progesterone receptor. The type was mostly invasive duct carcinoma, high grade (70.0%). Most of the tumor size ranged between 2-5 cm (56.9%), with more than 3 nodes in 38.3% of patients. High mitotic index was found in 69.5% and positive C-erbB-2 in 71.7% patients. Correlation of C-erbB-2 and other prognostic factors showed that only stage, node and mitotic index had significant correlations (p = 0.016; 0.035 and 0.005, respectively). A significant correlation was also found between ER and PR level, PR and tumor size, stage and tumor size, stage and nodes, tumor size and nodes (p < 0.05), and a borderline correlation between ER and tumor size (p = 0.065) in conclusion, this preliminary study showed that breast cancer in Yogyakarta had an aggressive phenotype. C-erbB-2 positivity was correlated significantly with stage of the disease, number of nodes involved and mitotic index. Hormone receptors also correlated with some prognostic factors in breast cancer patients.
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PMID:Correlation of clinical, pathological status, hormone receptor and C-erbB-2 oncoprotein in breast cancer patients. 1089 17

Simultaneous overexpression of c-erbB-2 and p53 has been reported to be prognostically unfavorable in breast cancer. Herein, we show that concurrent overexpression of these 2 proteins is associated with a marked reduction in the relative fraction of cells in G(1) phase of the cell cycle, indicating an accelerated cell cycle progression. Using an immunohistochemical approach, we examined 261 cases of node-negative infiltrating ductal carcinomas of the breast with respect to c-erbB-2 and p53 expression and to the proliferative activity measured by the Ki-67 index. By means of a novel monoclonal antibody, Ki-S2, which exclusively recognizes proliferating cells in the S, G(2), and M phases of the reproductive cycle, we were further able to calculate the relative fraction of the cells having passed the restriction point at the G(1)/S boundary, thus defining a cycling ratio (CR). The results were correlated with clinical outcome; median follow-up time was 96 months. Tumors that simultaneously overexpressed c-erbB-2 and p53 had a high median CR and followed an unfavorable course. However, increased CRs were also observed independently of c-erbB-2 and p53 overexpression, suggesting that other molecular mechanisms may contribute to acceleration of cell cycle progression. In a multivariate analysis that included patient age, tumor size, hormone receptor status, c-erbB-2 and p53 expression, and the Ki-67 index, CR emerged as the most significant independent predictor of overall and disease-free survival (P <.0001). It is concluded that the CR is a gauge of cell cycle deregulation and therefore may be a powerful indicator of the biologic behavior of cancers. HUM PATHOL 32:311-319.
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PMID:Concurrent overexpression of p53 and c-erbB-2 correlates with accelerated cycling and concomitant poor prognosis in node-negative breast cancer. 1127 41

The mutation of the p53 gene is a common phenomenon in numerous human tumors including breast cancer. It leads to an accumulation of nonfunctioning p53 protein in the cell nuclei, which can be detected by immunohistochemical techniques. In breast cancer overexpression of mutated p53 protein has been correlated to a poor prognosis. Our study is an immunohistochemical analysis of p53 in 82 cases of breast cancer in young (< or = 30 years old) Kuwaiti women, correlating it with histopathological grade, lymph node status, estrogen (ER) and progesterone receptor (PgR) content, tumor cell proliferation (immunostaining for Ki-67) and expression of c-erbB-2 oncoprotein. p53 immunostaining was found in 47 (57.32%) of the carcinomas. 65% of them displayed positive immunostaining for c-erbB-2. 63.7% of tumors with p53 overexpression were aneuploid. 64.8% of the p53 positive tumors were node positive. 93.5% of the p53 immunopositive carcinomas were ER-negative, and in 95.7% of this subclass of patients no PgR could be detected. The vast majority of p53 positive carcinomas were grade III (76.6%), 21.3% were grade II and 2.1% grade I, but neither tumor grade or tumor size showed a correlation with p53 expression. A significant negative correlation between ER- and PgR-content (p = 0.006) and immunostaining for p53 was observed. Our study provided evidence that the association of negative hormone receptor status and positivity for p53 immunostaining points to a greater tumor aggressiveness.
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PMID:Immunohistochemical detection of p53 protein expression in breast cancer in young Kuwaiti women. 1129 37

Every pathologist in active practice must be aware of and follow, set standards and recommendations for the diagnosis of breast carcinoma in order to ensure that the patient has the preconditions for an adequate therapy, regardless of the particular hospital setting. According to present-day knowledge, the standard obligatory examinations include conventional morphology (staging, typing and grading of the tumour) and the analysis of the steroid hormone receptor status (estrogen and progesterone). The immunohistochemical determination of tumour growth fraction with the Ki-67 antibody is economically justifiable, since it serves as an adjunct for histological/cytological tumour grading, a method that has a poor level of reproducibility. Since the introduction of herceptin immunotherapy, the determination HER-2/neu overexpression has gained a practical role and should now be included as an obligatory component of the diagnostic testing. Additional tumour markers are not components of routine diagnosis and these should be limited to clinical studies as long as their prognostic and therapeutic value have not been proven.
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PMID:[Current standards for the diagnosis of breast carcinoma in routine practice]. 1149 Sep 43

The HER-2/neu oncogene encodes a transmembrane receptor with intrinsic tyrosine kinase activity. A pilot study was performed to investigate downstream effects of HER-2/neu (or related growth factor receptor) activation by identifying phosphorylated tyrosine. Fifty-four breast carcinomas were evaluated for HER-2/neu overexpression by the HercepTest (Dako, Carpinteria, CA) and the monoclonal CB11 antibody (Ventana, Tucson, AZ). Phosphotyrosine (an indication of tyrosine kinase activity) was detected by an antiphosphotyrosine mouse monoclonal antibody (Upstate Biotechnology, Lake Placid, NY). The gene amplification status was evaluated in 50 of the 54 cases by fluorescence in situ hybridization (FISH) using the Ventana gene probe. The HER-2/neu oncogene amplification was detected in 28% (14 of 50) of cases. Of the 14 cases showing oncogene amplification, tyrosine kinase activity was detected in 9 (64.2%) cases. There was moderate agreement between HER-2/neu gene amplification and tyrosine kinase activity (kappa = 0.43). Immunohistochemical staining of 3+ (with both HercepTest and CB11) showed better agreement with HER-2/neu oncogene amplification and increased tyrosine kinase activity than 2+ immunohistochemical staining. Overall, oncogene amplification and overexpression correlated with increased tyrosine kinase activity, supporting the mechanism of tyrosine kinase activation by HER-2/neu amplification and overexpression. However, 7 cases showing increased tyrosine kinase activity did not show gene amplification or 3+ receptor expression (by either HercepTest or CB11), raising the possibility of other growth factor receptors operating via the tyrosine kinase pathway. There was no apparent correlation between tyrosine kinase activity and hormone receptor status (estrogen or progesterone). Increased tyrosine kinase activity is more commonly associated with higher-grade tumors and thus may correlate with aggressive biologic behavior in breast carcinoma. The results of this pilot study suggest that a larger-scale investigation into downstream activation of tyrosine kinase and correlation to clinical outcome or response to Herceptin therapy may identify subsets of patients whose clinical response or outcome may be predicted by tyrosine kinase activation.
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PMID:Tyrosine kinase activation in breast carcinoma with correlation to HER-2/neu gene amplification and receptor overexpression. 1177 67

The BRCA1 tumor suppressor gene and the HER-2/neu oncogene are located in close proximity on the long arm of chromosome 17 (17q11-21). Absence of BRCA1 or functional overexpression of the HER-2/neu gene presumably contributes to the somatic phenotype of breast cancer in premenopausal women, characterized by unfavorable prognostic features such as high tumor grade, hormone receptor negativity, and high proliferation rate. To examine whether amplification of HER-2/neu contributes to the aggressive biology of BRCA1-associated tumors, we have performed fluorescence in situ hybridization on formalin-fixed paraffin-embedded breast tumor tissue sections from 53 BRCA1 mutation carriers and 41 randomly selected, age-matched sporadic breast cancer cases. Although BRCA1-associated and sporadic tumors were equally likely (19% versus 22%) to exhibit HER-2/neu amplification [defined as a ratio of HER-2/neu copies to chromosome 17 centromere (CEP17) copies > or = 2], 6 (15%) of the sporadic tumors were highly amplified (defined as a ratio greater-than-or-equal 5) versus none of the BRCA1-associated tumors (P = 0.048). HER-2 protein overexpression as measured by immunohistochemical analysis was not observed among the BRCA1-associated cases (P = 0.042). Four of 21 (19%) sporadic tumors exhibited strong membranous staining of HER-2 (intensity level of 3+) as compared with 0 of 39 BRCA1-associated tumors. Our data suggest that a germ-line mutation in the BRCA1 tumor suppressor gene is associated with a significantly lower level of HER-2/neu amplification. Thus, it is possible that BRCA1-associated and HER-2/neu-highly amplified tumors progress through distinct molecular pathways, and the aggressive pathological features of BRCA1-associated tumors appear unrelated to amplification of the adjacent HER-2/neu oncogene.
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PMID:Molecular-cytogenetic analysis of HER-2/neu gene in BRCA1-associated breast cancers. 1188 24

The aim of this study was to analyse the relationships between the expression of c-erbB-2, estrogen receptor (ER), progesterone receptor (PR), Bcl-2 and PCNA in node negative breast cancer. Expression of these markers was determined by HercepTest, by immunohistochemistry and quantified by morphometry in the group of 125 selected breast carcinoma patients with broad spectrum of histological types and grades. Multivariate statistical analysis revealed only relationships between ER/PR, ER/Bcl-2, ER/grade and ER/age. There was not found any significant relationship between c-erbB-2 expression and any other immunohistochemical marker, apocrine metaplasia, histological type or patient characteristics. The same result was found in complete group of tumors as well as in individual groups divided according to histological type. These results indicate that in node negative breast tumors, c-erbB-2 expression does not correlate inversely with hormone receptor status and hormone responsiveness like previously reported metastasising breast cancer and that the prognostic significance of c-erbB-2 expression in these tumors is not clear.
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PMID:Expression of c-erbB-2 in node negative breast cancer does not correlate with estrogen receptor status, predictors of hormone responsiveness, or PCNA expression. 1208 2

Prediction of outcome and individualization of therapeutic strategies are challenging problems in oncology. Predictive parameters for response to hormonal treatment include the expression of hormone receptor, the extent and location of metastatic spread, disease-free interval, patient age, response to prior hormonal therapy, grading, and more recently, some molecular markers like the expression of HER-2/neu. The use of conventional statistics for prediction of response to hormonal treatment is limited by non-linearities and complex interactions between predictive factors. Modern computational mathematical models like artificial neural networks, entropy-based inductive algorithms or chi(2) interaction detection algorithms can describe these interactions and generate classification models and decision structures. They can be used to predict the clinical outcome for individual patients. In contrast to conventional methods, the level of confidence for the predictions can reach 90% and more. This might be an important step towards further individualization of therapeutic strategies.
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PMID:Prediction of response to hormonal treatment in metastatic breast cancer. 1241 85

HER-2/neu overexpression occurs in a proportion of invasive breast carcinomasand is an adverse prognostic indicator, although its apparent strength as a prognostic indicator varies in different studies. Paradoxically, HER-2/neu is overexpressed with particularly high frequency in ductal carcinoma in situ (DCIS). We have hypothesized and presented supporting data that HER-2/neu is actively signaling in a subset of the tumors in which it is overexpressed. We use an activation state-dependent anti-HER-2/neu monoclonal antibody (PN2A) produced in our laboratory to study this paradigm immunohistochemically. In this report, we analyze the characteristics of 219 cases of DCIS with respect to HER-2/neu expression and activation state. We find that 58% of cases of DCIS with overexpression have the receptor in the activated state, a substantially greater proportion than we have previously noted for invasive carcinomas. Although HER-2/neu overexpression in general was inversely correlated with hormone receptor expression, cases with activated HER-2/neu had the lowest hormone receptor positivity rate. Statistically significant correlations with activated HER-2/neu were not noted for tumor size, presence of calcifications, necrosis or fibrosis, or indicators of angiogenesis. These results suggest that examination of activated HER-2/neu status may better reflect the biology of a tumor than overall determination of HER-2/neu levels. Our finding that active signaling by HER-2/neu, as detected by this assay, is more frequent in DCIS than previously noted for invasive carcinoma implicates signaling by HER-2/neu as having a critical role in the early stages of breast tumorigenesis.
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PMID:Active signaling by HER-2/neu in a subpopulation of HER-2/neu-overexpressing ductal carcinoma in situ: clinicopathological correlates. 1243 65

The first part of this two-part review of established and emerging breast cancer biomarkers and molecular diagnostics considers breast cancer predisposition, screening tests for diagnosis, diagnosis using small specimens and metastatic lesions, micrometastatic disease and breast cancer prognosis assessment. Prognostic factors covered in this review include: cytogenetic markers, DNA ploidy and S phase determination, cell proliferation markers, cell cycle regulators and growth factor measurements including epithelial growth factor receptor, HER-2/neu and a variety of other relevant molecules controlling proliferation, differentiation and angiogenesis. The first section of part two will continue the consideration of breast cancer prognostic factors including oncogenes, tumor suppressor genes, cell adhesion molecules, invasion-associated proteins and proteases, hormone receptor proteins, drug resistance proteins, apoptosis regulators, transcription factors, telomerase, DNA repair and methylation and transcriptional profiling using high-density genomic microarrays. The second section of part two will consider the prediction of therapy response using the techniques of pharmacogenetics and pharmacogenomics.
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PMID:Breast cancer biomarkers and molecular medicine. 1451 Jan 78


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