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)

Overexpression of the ERBB-2 protein has become a target of the anti-neoplastic treatment in patients with invasive duct carcinomas of the breast with a monoclonal antibody trastuzumab (Herceptin, Genentech). From this reason the immunohistochemical (IHC) evaluation of ERBB-2 protein expression is crucial. However, there are patients in whom the IHC investigation is biased by a subjective evaluation among cases considered negative (in the range of 1+) and positive (2+), and among cases considered positive 2+ and 3+. In such cases it is advisable to complement the IHC investigation by detection of copy numbers of the ERBB2 gene with fluorescence in situ hybridization (FISH). The overexpression of the protein is caused by the gene amplification in a majority of cases. The patients, whose carcinomas show overexpression of the ERBB-2 protein and the overexpression is caused by a significant gene amplification, profit from the Herceptin therapy. In this review we focus also on the methodology of FISH in paraffin sections and tissue imprints with respect to the detection of copy numbers of chromosome 17 and the ERBB2 gene.
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PMID:[Indications for treatment in invasive ductal carcinoma of the breast with Herceptin from the aspect of laboratory diagnosis--study of the ERBB-2 protein and determination of the number of copies of the ERBB2 gene. Review]. 1267 91

This minireview covers the key data on biology and clinical implications of the c-erbB-2 oncogene in breast and prostate cancer. The aim was to provide basic information to practically oriented pathologists in order to make a reasonable application of methods for c-erbB-2 overexpression or amplification analysis. The clinical interpretation of c-erbB-2 abnormalities should reflect the complexity of c-erbB-2 mediated regulatory pathway and explain why tumours with overexpression/amplification of c-erbB-2 very often do not respond to therapy using Herceptin.
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PMID:[What is the real importance of evaluating the expression of c-erbB-2 (HER-2/neu) in carcinoma of the breast and prostate? (A short review)]. 1267 92

Routine assessing of HER2 status is necessary for successful treatment of carcinoma of breast by Herceptin. Our results prove comparability of well standardized semiquantitative method by Hercep Test DAKO: both negative findings (73.4% in laboratory A, and 77.4% in laboratory B) and positive findings (26.6% in laboratory A, and 22.6% in laboratory B) corresponded both with each other and with the DAKO's reference data. The study also testifies to problems with interpretation of the IHC data (primary antibody c-erbB-2-oncoprotein DAKO). The problems concern particularly the processing standards, the dilution of antibodies, the application of IHC automatic machine, and probably also the detection system. It is suggested that each laboratory develops a standardized IHC protocol, in coordination with other laboratories. Thus, standardization of both processing and evaluation of the results will be achieved. As the indication for treatment by Herceptin is connected with HER2 overexpression, it is suggested to follow the algorhythm of HER2 examination presented by Nenutil at the ROCHE Satellite symposium.
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PMID:[Immunohistochemical detection of HER2 protein and its evaluation in breast carcinoma: comparative study of two methods (HercepTest DAKO versus the routine immunohistochemical approach with the DAKO polyclonal antibody) and the results from two laboratories]. 1267 93

Sarcomas currently represent 1% of adult malignancies and 15% of pediatric malignancies. To determine the prevalence of HER-2/neu overexpression by the histologic type and to identify a possible predictive role in patients with sarcoma, we performed a retrospective study on subjects with a biopsy-proven diagnosis of a soft tissue sarcoma. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of 2+ or greater was considered positive for overexpression. Two hundred seventy-three patients with soft tissue sarcoma were identified (164 females, 109 males) with a mean age of 56 (range: 1-93). The most common tumors identified were malignant fibrous histiocytoma (MFH) (18.3%), dermatofibrosarcoma (DFS) (16.1%), leiomyosarcoma (13.2%) and carcinosarcomas (CS) (7.3%). Of the 273 specimens, 29 (10.6%) revealed HER-2/neu overexpression. CS, MFH, and DFS specimens showed the highest incidence of HER-2/neu overexpression (40%, 26%, and 18.2%, respectively). The incidence of HER-2/neu overexpression was found to be significantly higher in patients with a survival of less than 8 months (p = 0.035). This demonstrates that HER-2/neu overexpression is preferentially seen in certain soft tissue sarcomas, and when present is associated with a poorer prognosis in patients with sarcoma. Further studies would delineate whether HER-2/neu overexpression renders sarcomas chemoresistant and thus adversely affects outcome. In addition, there may be a role for Herceptin (trastuzumab) alone, or in combination with conventional therapy, in patients with CS, MHF, and DFS.
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PMID:HER-2/neu overexpression detected by immunohistochemistry in soft tissue sarcomas. 1271 94

To investigate the prognostic value of Her2/neu expression in differentiated thyroid carcinomas 103 patients were retrospectively investigated. All of them received surgical and an identical follow-up treatment. The patients with papillary and follicular thyroid cancer were further separated into two groups concerning their clinical development, including one group without distant metastasis (follow-up of minimum 8 years). The second group presented with distant metastases as a sign of an aggressive behaviour. Her2/neu was immunohistochemically detected on sections from formalin-fixed, paraffin-embedded tissues using c-erbB-2/Her-2/neu oncoprotein Ab-17 monoclonal antibody (mAb). In statistical analysis using the Mann-Whitney U-test and chi(2) test, Her2/neu protein overexpression was significantly correlated with prognosis. Both tumour entities without distant metastases showed significantly less cytoplasmic immunostaining than patients with development of metastases. Concerning the clinical outcome, Her2/neu overexpression may be regarded as a prognostic factor in differentiated thyroid carcinomas. Moreover, in addition to standard radio-iodine elimination therapy, application of Herceptin could lead to new successful therapeutic concepts for a number of patients with progressive thyroid cancer.
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PMID:Her2/neu overexpression in differentiated thyroid carcinomas predicts metastatic disease. 1271 68

The amplification and/or overexpression of the HER-2/neu oncogene and its encoded receptor protein are increasingly used for prognostication and prediction of therapeutic response to Herceptin in breast cancer. However, large-scale examination of archival tumor blocks by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) is prohibitively laborious and technically challenging. The tissue microarray (TMA) technique enables hundreds of tumors to be studied simultaneously in a single experiment. To evaluate the HER-2/neu status of a selection of the breast tumors in our tumor bank, we constructed a TMA from 97 breast tumors, with a single 0.6-mm core per specimen. HER-2/neu gene amplification by FISH was found in 20 of the 87 interpretable cases (23%): in 14 of 14 IHC 3+ cases (100%), 5 of 8 IHC 2+ cases (62.5%) and 1 of 65 IHC 0/1+ cases (1.5%). Three of the 67 cases with no evidence of HER-2/neu gene amplification by FISH were moderately positive (2+) by IHC. A close relationship was observed between these 2 assays as applied to the TMA (95.4% concordance: 95% CI, -2.2% to 6.8%; P <0.0001), and both HER-2/neu gene amplification and protein overexpression were strongly associated with tumor grade, estrogen receptor status, and progesterone receptor status. Gene amplification was found in most of the tumors with high-level overexpression (IHC 3+) and not in the unequivocal IHC-negative cases. Complementary analysis by IHC and FISH are, however, recommended for tumors graded as 2+ by IHC, the group with the most result discrepancy. Hum Pathol 34:362-368.
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PMID:Evaluation of HER-2/neu oncogene status in breast tumors on tissue microarrays. 1273 17

The clinical role of HER-2/neu, a 185 kD epithelial transmembranous protein, has evolved after the approval of the anti-HER-2/neu targeted monoclonal antibody trastuzumab (Herceptin) for the therapy of metastatic breast cancer. The extracellular domain of HER-2/neu undergoes proteolytic cleavage from the full-length protein by metalloproteases, and is shed into the blood as a circulating antigen. While HER-2/neu gene amplification and/or protein overexpression are detected in approximately 25% of primary breast cancers, serum HER-2/neu levels are elevated beyond the upper limit of normal in 50 to 60% of stage IV breast cancer patients. HER-2/neu in serum can be detected by enzyme immunoassays (manual and automated versions). It has been shown to have prognostic and predictive information in breast cancer patients. Monitoring for recurrence by serum HER-2/neu reaches a high sensitivity for HER-2/neu positive tumors. Longitudinal follow-up of patients during any kind of systemic therapy allows for monitoring of the therapeutic success. When utilized in these applications, serum HER-2/neu testing is complementary to HER-2/neu tissue results and to the determination of classical tumor markers such as CA 15-3, CA 27.29 and CEA, which are not targeted by specific forms of systemic therapy.
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PMID:Serum HER-2/neu in the management of breast cancer patients. 1281 Jan 50

The HER-2/neu oncogene codes a protein of the family of epidermal growth factor receptors. The extracellular domain has a MW from 95-105 kDa and is shed into the blood. In some patients with malignant tumors there is a high expression of HER-2/neu connected with high levels of HER-2/neu protein in the serum. High concentrations signal aggressive growth, bad prognosis and shorter survival. The reference range lies between 4.0 and 14.0 ng/ml with a mean of 9.0 ng/ml. There is a significant difference of values between patients with and without metastases, but not between healthy people and patients without metastases. The advantage of this parameter lies in the early diagnosis of recurrence in the therapy of metastasizing breast carcinomas especially on treatment with Herceptin.
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PMID:HER-2/neu gene product in serum--an oncoprotein in the diagnosis and therapy of breast carcinoma. 1282 Mar 39

In this study we describe and discuss the dichotomous effects of docetaxel trastuzumab (Herceptin)/docetaxel therapy on the angiogenic molecular profile in two patients with her-2 + chemo-resistant recurrent breast carcinoma. In the first case, an intensification of angiogenesis occurred following therapy, accompanied by an impressive increase of the cancer cell proliferation index. This tumor did not express HIF1 alpha and shared a HIF-independent VEGF overexpression, which remained unaffected by therapy. An intensified formation of thymidine phosphorylase (TP)-rich stroma, presumably a response to docetaxel, shows a TP-dependent angiogenic response. In the second patient, VEGF and HIF1 alpha were down-regulated in post-treatment biopsies and this was accompanied by a sharp reduction of the vascular density and of the cancer cell proliferation rate. In both cases, c-erbB-2 expression was abrogated by Herceptin. Taking into account that Herceptin down-regulates VEGF through reduction of HIF1 alpha synthesis, this clinical study provides evidence that an anti-angiogenic effect from Herceptin/Docetaxel therapy is expected only in tumors with HIF1 alpha-dependent VEGF overexpression. In contrast, HIF1 alpha-independent VEGF angiogenic activity cannot be abrogated by Herceptin. Docetaxel mediated up-regulation of TP in the tumoral stroma may, on the contrary, result in angiogenesis intersification and rapid tumor relapse. Such an effect should be of clinical importance since Herceptin/Docetaxel-based regimens are currently evaluated for the adjuvant therapy of her-2 + breast cancer patients. Studying the Herceptin-induced phenotypic changes of tumors could lead to the identification of specific molecular profiles that bring about diverging angiogenic responses. Adjustment of the chemotherapy regimen accordingly would prove of clinical importance.
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PMID:The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status? 1282 Apr 39

EGFr/HER1 and c-erbB-2/HER2 expression are associated with poor prognosis in breast cancer. The type I receptor tyrosine kinase (RTK) family to which they belong has four members (HER1-4). In this study, expression of HER1-4 and oestrogen receptor (ER) expression were determined by immunohistochemistry in 220 breast carcinomas. Elevated expression of HER1 was observed in 16.4%, HER2 in 22.8%, HER3 in 17.5%, and HER4 in 11.9% of these tumours. Patients whose tumours overexpressed HER1, 2 or 3 had reduced survival (p= <0.001), whereas those whose tumours overexpressed HER4 had increased survival (p=0.013); 38.6% of cases overexpressed one or more of HER1, 2 or 3. HER4 was rarely overexpressed with other HERs (1.4% of cases). Cox's multiple regression analysis demonstrated that overexpression of HER1/2/3, HER4, and standard prognostic indicators independently affected survival. HER1-3 expression was related to ER negativity (p<0.0001, chi2). Patients with ER-positive, HER1-3-positive tumours had a significantly poorer survival (p<0.001) than those with ER-positive/HER-negative or HER4-positive tumours. Expression of HER RTKs displays complex interactions between different family members. There is a strong interaction, in terms of survival, between HER expression and ER expression. The development of HER-targeted agents (eg Herceptin, Iressa), and agents targeted at the downstream signalling pathways, therefore provides new possibilities in the treatment of breast cancer.
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PMID:Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. 1284 22


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