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)

Secretory carcinomas (SCA) are distinguished from infiltrating ductal carcinomas (IDC) of the breast by their characteristic histomorphology and more favorable prognosis and by the expression of a chimeric tyrosine kinase that is encoded by the ETV6-NTRK3 fusion gene. On this basis, we evaluated 13 SCAs (12 of them with ETV6-NTRK3 gene fusion) by molecular and immunohistochemical (IHC) methods. DNA was obtained from 8 of 13 microdissected SCAs and was analyzed for genetic alterations (GA) by comparative genomic hybridization (CGH). IHC staining was performed for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67 (MIB1) in all 13 cases. Molecular and immunohistochemical results in SCAs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. An average of 2.0 GAs (range: 0 to 6) were detected, including recurrent gains of chromosome 8q (37.5%) and 1q (25%) and losses of 22q (25%). Four of 13 (31%) SCAs were positive for ER, and 2 were positive for PR. The mean MIB1-labeling index was 11.4% (range: <1 to 34%). Her-2/neu protein overexpression was detected in 2 cases, including 1 with strong (score 3+) and 1 with weak HER2/neu expression (score 2+). Fluorescence in situ hybridization analysis of the latter case showed no evidence of HER-2/neu-gene amplification. Compared with previous findings in IDCs, SCAs are characterized by a relatively low number of GAs, a low proliferative rate, infrequent HER2/neu protein overexpression, decreased steroid hormone receptor expression, and expression of ETV6-NTRK3 fusion gene. These results support the hypothesis that SCAs have immunohistochemical and genetic features that distinguish them from IDCs of the usual type.
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PMID:Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry. 1469 16

Breast cancer is associated with increased glucose consumption and can therefore be visualised with the glucose analogue [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) and positron emission tomography (PET). FDG uptake in the primary tumour can vary substantially, and specific tumour characteristics have been demonstrated to determine the degree of glucose metabolism. Factors with a major influence on FDG uptake in breast cancer comprise expression of glucose transporter Glut-1 and hexokinase I, number of viable tumour cells per volume, histological subtype, tumour grading, microvessel density and proliferative activity. Recently, an association between high FDG uptake and a worse prognosis was suggested. Several studies have been performed correlating FDG uptake with a variety of prognostic and molecular biomarkers as well as parameters predicting tumour response to therapy. However, a correlation with important clinical prognostic markers such as axillary lymph node status and size of the primary tumour, expression of oestrogen and progesterone receptors, proto-oncogene c-erbB-2 or VEGF could not be demonstrated. The lack of correlation with important markers of prognosis does not suggest that FDG uptake might be used as a prognostic criterion in breast cancer. Innovative radiotracers for specific imaging of tumoural perfusion ([(15)O]H(2)O), hormone receptor expression ([(18)F]FES), protein synthesis ([(11)C]methionine), proliferation rate ([(18)F]FLT) or bone mineralisation ([(18)F]fluoride) may provide additional information compared with that provided by FDG PET.
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PMID:Biological characterisation of breast cancer by means of PET. 1512 40

The C-erbB-2 proto-oncogene encodes a 185KD glycoprotein with tyrosine kinase activity. Overexpression of this gene either due to gene amplification and/or increased transcription has been observed in a variety of cancers and has been associated with more aggressive disease and a poor clinical prognosis in 20-30% of patients with breast cancer. Besides several prognostic factors like tumor size, histologic grade, steroid hormone receptor status, DNA ploidy, lymph node status etc which are significant in the management of breast cancer, C-erbB-2 status might also serve as an additional parameter. Immunohistochemistry is the most widely used method to study the expression of C-erbB-2 in breast cancer. The very low levels of expression of C-erbB-2 by normal tissues makes this receptor, a potential target for diagnosis and therapy with monoclonal antibodies raised against its extracellular domain. One such monoclonal antibody designated as CIBCgp185 of IgG2a isotype has been generated in our laboratory and extensively characterized. In the present study, an indirect immunohistochemical assay was carried out on frozen tumor tissue sections of 127 malignant breast tumor specimens of various histological types using monoclonal antibody CIBCgp185, which revealed intense staining of tumor cell membrane in 32 specimens, indicating overexpression of C-erbB-2. In the case of 53 benign breast tissues and 24 normal breast tissues studied, this MAb did not exhibit any reactivity. These results suggest that MAb CIBCgp185 might prove useful to identify tumors with overexpression of C-erbB-2 which are often associated with poor prognosis and early recurrence and might have future therapeutic application in the treatment of these cancers.
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PMID:Immunohistochemical assay (IHC) to study C-erbB-2 status of breast cancer using monoclonal antibody CIBCgp185. 1515

The mechanisms mediating the proliferative effects of gastrointestinal (GI) peptide hormones and their cognate G protein-coupled receptors are associated intimately with epidermal growth factor (EGF) receptor-regulated signaling pathways. Although transactivation of the EGF receptor is now recognized as a critical component in GI peptide hormone regulation of mitogenic signaling and cell migration, their interactions are far more complex and include potentiation of intracellular signaling pathways, regulation of ligand expression and release, and modulation of cell surface receptor expression. Mitogen-activated protein kinases play a central role integrating the signals from these receptor systems. This review summarizes the mechanisms that intertwine GI peptide hormone receptor- and EGF receptor-activation and functions.
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PMID:Bi-directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor. 1562 29

In order to make optimal treatment recommendations for patients with early-stage breast cancer, it is essential to accurately determine the patient's underlying risk of disease recurrence and choose a therapy to which the individual is most likely to respond. Lymph node status, tumor size, histopathologic features including tumor type and grade, and hormone receptor status are well-accepted prognostic factors related to breast cancer. In addition, hormone receptor status is a very strong predictor of response to hormonal therapy. However, our currently accepted prognostic and predictive factors fall short and there is a critical need to more accurately identify those most likely to require or benefit from particular therapies. Attention has therefore focused on the determination of novel prognostic and predictive factors. The most promising new factor is the level of urokinase plasminogen activator and its inhibitor plasminogen activator inhibitor. Other putative factors include proliferative rate, the presence of lymphatic or vascular invasion, human epidermal growth factor receptor 2 (HER-2/neu or erbB-2) positivity, the presence of micrometastases in lymph nodes or bone marrow, and gene expression profile by microarray analysis, and by RNA-based methodology. Data regarding potential new prognostic factors are constantly emerging. These studies are frequently challenging to interpret as they are often retrospective, based on relatively small numbers of patients, include a mix of treated and untreated women, and often do not control for other known prognostic factors. Therefore, new data must be interpreted with caution.
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PMID:Utilizing prognostic and predictive factors in breast cancer. 1571 96

Endometrial adenocarcinoma is the most common malignant neoplasm of the female genital tract and, despite its relative frequency, the molecular events that contribute to the development and progression of the lesion remain poorly understood. The normal human endometrium is characterized by hormone-dependent variations during the menstrual cycle. This tightly controlled system is disturbed in endometrial hyperplasia and carcinomas and a series of changes initiate and promote progression towards the malignant phenotype. These changes can be subdivided into discrete steps, involving activation of oncogenes, inactivation of tumour suppressor genes, deregulation of cell cycle regulators or other proteins involved in tumour invasion and progression. Immunohistochemical expression of different biomarkers such as hormone receptor status (ER, PR), proliferation associated indices (PCNA, MIB1), oncogene (c-erbB-2), tumour suppressor gene products (pRb, p53 protein), cell cycle related proteins (cyclin D1, cyclin E, p21/WAF1), anti-apoptotic protein (bcl-2), adhesion molecule (CD44s), proteolytic enzyme (cathepsin D), heat shock protein (hsp27) and metallothionein (MT) has shown the contribution of these molecules to endometrial carcinogenesis in a hormone-dependent or independent manner as an early or late event. In addition, these biomarkers seem to be correlated with tumour differentiation or myometrial invasion, and therefore could be considered as indicators of the biological behaviour of endometrial carcinoma. Furthermore, the interrelationships of these molecular markers show that these genetic dysregulations could be implicated in the control of cell proliferation and differentiation, and thereby in the multistep process of endometrial carcinogenesis.
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PMID:Immunohistochemical tumour markers in endometrial carcinoma. 1612 80

Patients with human epidermal growth factor receptor 2 (HER-2) overexpressing breast carcinomas have a more aggressive clinical behavior and their tumors are often hormone receptor negative. However, the recently introduced anti-HER-2 antibody trastuzumab has been proven to improve the survival and controls the disease in a significant proportion of these patients. Therefore, the analysis of HER-2 in patients with breast cancer has become an important and routine test to select those who may benefit from the gene-based targeted therapy trastuzumab (herceptin). There is good correlation between HER-2/neu protein overexpression and HER-2 gene amplification in breast cancer. However, inconsistent results have been reported in the rate of HER-2/neu protein overexpression in other malignant neoplasms. Furthermore, only rare studies have investigated the correlation between the HER-2/neu protein overexpression and the status of HER-2 gene in these tumors. We investigated the HER-2 gene and protein status in several cases of Paget disease of the nipple and vulva by using a chromogenic in situ hybridization assay and immunohistochemistry. We find that the majority of the Paget disease of the breast demonstrate HER-2 gene amplification, whereas most of the extramammary Paget disease lack HER-2 gene amplification. In addition, our results show a good correlation between HER-2/neu protein overexpression and HER-2 gene amplification in Paget disease of the nipple, but we were unable to confirm this correlation in HER-2/neu protein overexpressing Paget disease of the vulva.
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PMID:HER-2 gene amplification in Paget disease of the nipple and extramammary site: a chromogenic in situ hybridization study. 1693 67

The association between the polymorphism of the angiotensin-converting enzyme (ACE) gene and breast cancer risk has been extensively studied, however, the studies about the prognostic factors and ACE gene polymorphism are limited in number. Our aims were to analyze the distribution of the insertion/deletion (I/D) polymorphism of the ACE gene in Turkish premenopausal patients with breast cancer, which is more aggressive than the postmenopausal counterpart, and to assess whether DD genotype is associated with poor prognostic factors. The DD genotype has been shown to be associated with the increased serum and tissue levels of ACE, compared to those in II and ID genotypes. ACE genotypes were determined by polymerase chain reaction in 44 Turkish premenopausal patients with breast cancer and in 46 age-matched healthy premenopausal women. ACE genotypes are distributed in patients and control subjects as follows; DD is present in 25 (56.8%), ID in 17 (38.6%), and II in 2 (4.5%) patients, and DD in 28 (60.9%), ID in 12 (26.1%), and II in 6 (13.0%) healthy subjects, respectively. D and I alleles were found in 76.1% and 23.9% of the patients, while 73.9% and 26.1% in healthy subjects, respectively. In breast cancer patients, no significant association was observed between the ACE genotypes and poor prognostic factors, such as negative hormone receptor status, histological grade, lymph node involvement, higher number of lymph node metastases, and c-erb B2 overexpression, except that tumor size greater than 2 cm is associated with DD genotype (p = 0.02). Thus, ACE may influence the local tumor growth of breast cancer in premenopausal patients.
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PMID:Association between the polymorphism of the angiotensin-converting enzyme gene and tumor size of breast cancer in premenopausal patients. 1702 64

The anti-apoptotic molecule, Bcl-2, is well known to play an important role in the chemoresistance of breast cancer. We have previously demonstrated that phosphorylation of Fas-associated death domain-containing protein (FADD) at 194 serine through c-jun NH2-terminal kinase (JNK) activation sensitizes breast cancer cells to chemotherapy through accelerating cell cycle arrest at G2/M, and that Bcl-2 phosphorylation downstream of JNK/FADD plays an important role in cell growth suppression by paclitaxel. In this study, the clinicopathological association of phosphorylated Bcl-2 (P-Bcl-2) with estrogen, progesterone, c-erbB-2 receptors, p53 expressions and phosphorylated FADD/JNK (P-FADD/JNK) was analyzed immunohistochemically using 107 human breast cancer specimens. Expression of P-Bcl-2 was found to significantly correlate with lymphatic invasion, lymph node metastasis, but not histological differentiation, tumor grade or vascular and fatty invasion. The positivity of P-Bcl-2 was also significantly correlated to that of P-FADD/JNK. Thus, P-Bcl-2 as well as the P-FADD/JNK parameter might be useful markers for cancer progression, independent of the hormone receptor status, in human breast cancers.
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PMID:Bcl-2 phosphorylation has pathological significance in human breast cancer. 1711 50

Most women with breast cancer that overexpresses either estrogen (ER+) or progesterone receptors (PR+) will be treated with an endocrine agent. Although ER and PR are the only validated predictive markers of response to hormonal therapy, many women with hormone receptor-positive (HR+) tumors will fail to respond to endocrine treatment or develop hormone resistant disease. Another tumor marker, HER-2/neu, is an oncogene whose amplification or protein overexpression predicts response to a monoclonal antibody targeting HER-2/neu, as well as to anthracycline-based chemotherapy. Preclinical and some clinical data suggest that HER-2/neu positivity may also predict for relative resistance to endocrine therapy. Interpretation of clinical data addressing this issue is confounded by largely retrospective study designs and considerable heterogeneity in patient populations and methods of marker detection and interpretation. At this writing, HER-2/neu expression should not influence the decision to use endocrine therapy.
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PMID:Selecting endocrine therapy for breast cancer: what role does HER-2/neu status play? 1714 48


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