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)

Novel palliative strategies for patients with androgen-independent prostate cancer (AIPC) include targeting the epidermal growth factor receptor (EGFR) family. The aim of the present study was to investigate intrapatient changes of EGFRs during the development of AIPC. In total, 106 symptomatic AIPC patients were identified in whom prostatic biopsies (adenocarcinoma) were available both before the start of androgen deprivation (PRTR biopsy) and after the development of AIPC (AIPC biopsy). All four known subgroups of the EGFR family were determined by immunohistochemistry (IHC): c-erbB-1 (EGFR), c-erbB-2 (HER2/neu), c-erbB-3 (HER3) and c-erbB-4 (HER4). Moderate to strong membrane-specific staining was recorded semiquantitatively (<10% vs >/=10%=IHC stained tumour cells: 'negative' vs 'positive' staining). The medical records were reviewed for clinical variables. During the development of AIPC, intrapatient changes occurred in two opposite directions for each of the four EGFRs: negativity changed to positivity, and vice versa, statistically significant only for the increase of c-erbB-1 expression (P=0.001). The c-erbB-2 expression in the AIPC biopsy was associated with a significantly shorter survival from the time of the AIPC biopsy (P=0.029). Our results support ongoing therapeutic attempts of EGFR inhibition in subgroups of patients with prostate cancer. Further research is needed to understand the function of EGFRs in this malignancy.
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PMID:Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence. 1473 92

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero- and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours co-expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.
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PMID:Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma. 1548 Apr 34

Large-core needle biopsies are frequently used for the preoperative evaluation of the breast lesions. In addition to initial diagnostic information, they can show the status of molecular markers with predictive and prognostic value and further contribute to an optimal selection of treatment strategy. So far, the potential use of large-core needle biopsies in assessment of marker profile of the breast lesions was studied using the immunostaining approaches. In this work, we sought to determine whether analysis of the large-core needle biopsy by semi-quantitative reverse-transcription polymerase chain reaction reveals molecular data that correspond with the marker status of the subsequently removed tumor. Five molecular markers including ER, PR, c-erbB-2/HER-2/neu, c-erbB-3/HER-3, and CD44 were assessed on mRNA isolated from 23 large-core needle biopsies and corresponding surgical breast cancer specimens using beta2- microglobulin as an internal standard. Significant or highly significant correlation between core biopsies and excised tumors was observed for each marker when the mRNA expression status was scored as positive or negative, with the concordance of the data ranging from 73.9% to 86%. Using the dichotomous scoring, majority of the biopsies (75%) displayed molecular profile that was either identical to the profile of the related tumor specimen, or with the difference in one marker. However, no significant correlation was found when the levels of the markers were expressed as continuous variables, possibly due to intratumoral cell heterogeneity. These results suggest potential usefulness and reliability of semi-quantitative RT PCR in the evaluation of large-core needle biopsies with regard to marker positivity or negativity. On the other hand, the marker-related data expressed as continuous variables cannot be accurately assessed on the large- core needle specimens using this approach, indicating the need for methodological improvements.
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PMID:Semi-quantitative RT-PCR assessment of molecular markers in breast large-core needle biopsies. 1564 Sep 49

Overactivation of epidermal growth factor receptor (EGFR) signaling has been recognized as an important step in the pathogenesis and progression of multiple forms of cancer of epithelial origin. Reports regarding EGFR family members in brain tumors are sparse and, thus, the significance of EGFR expression in childhood brain tumors is unclear. In this study, the expression of the EGFR family members was analyzed in 22 medulloblastomas. During the immunohistochemical study, a sensitive, four-step, alkaline phosphatase conjugated antigen detection technique was employed. The results demonstrated the presence of c-erbB-2 (HER-2) and c-erbB-4 (HER-4) in 10 to 50% of the neoplastic cells of high-grade glial tumors with high immunoreactivity, while c-erbB-3 (HER-3) was only detected in less than 10% of the neoplastically-transformed cells. In a follow-up, 70% of children, usually under 4 years of age, with c-erbB-2 (HER-2)-positive MEDs/PNETs, succumbed to the cancer. The Kaplan-Meier estimation revealed a significant correlation between c-erbB-2 expression and survival (p = 0.002), suggesting that c-erbB-2 (HER-2) is probably a prognostic marker for limited survival. Medulloblastoma is the most common malignant brain tumor that occurs during childhood. Multimodality treatment regimens have substantially improved survival in this disease; however, the tumor is incurable in about one-third of patients with medulloblastoma, and the current treatment has a detrimental effect on long-term survivors. As such, the results of this study further support the idea that targeting EGFR alone, or in combination with its downstream mediators, represents a promising new approach for the management of childhood brain tumors. Moreover, c-erbB-2 (HER-2) expression may also be of use in better classifying brain tumors.
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PMID:Epidermal growth factor receptor (EGFR) expression in childhood brain tumors. 1609 49

The intention of the present study was to assess immunohistochemically the expression of c-erbB receptor family in cervical carcinoma specimens of young women. Simultaneously, HPV was detected in the same specimens using immunohistochemical assays. Seventy-five cervical intraepithelial and invasive cancer specimens were assessed retrospectively. Positive c-erbB-2 immunostaining was revealed in 11.7% of tumor specimens, while for c-erbB-3 and c-erbB-4 receptor the corresponding figures were 32% and 49.3%, respectively. Concerning HPV infection-markers, positive immunostaining was found in 31% of cases, while coilocytes were detected in 64% of patients. The correlation of c-erbB receptor expression with malignant aggressiveness in cervical cancer cells concurs with similar data regarding other neoplasias, thus rendering these receptors an important predictive factor and future therapeutic target.
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PMID:Immunohistochemical detection of HPV proteins and c-erbB receptors in cervical lesion specimens from young women. 1655 Sep 74

The expression of c-erbB receptors was immunohistochemically examined in paraffin embedded specimens from non-small-cell lung carcinomas. A total of 209 patients were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large-cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit scoring guidelines were used for the interpretation of positivity. C-erbB-1 was overexpressed in older patients, in squamous-cell carcinomas and in poorly-differentiated tumours, whereas c-erbB-2 overexpression with adenocarcinomas and poorly-differentiated tumours. C-erbB-4 overexpression correlated with advanced disease stage. The c-erbB-1/4 pair was the most commonly overexpressed and significantly correlated with female gender, while the c-erbB-1/2 pair with older age. Response to chemotherapy was significantly reduced in patients with tumours overexpressing c-erbB-1 receptor as well as the c-erbB-1/2 and c-erbB-3/4 receptor pairs. Patients' overall survival was significantly correlated with the co-expression of c-erbB-1 and c-erbB-4 receptors. These findings clearly suggest that specific receptors overexpression or co-overexpression is correlated with patients' disease control rate and outcome. A better understanding of the overexpression of the heterodimerized partners of c-erbB family receptors may provide a useful predictive indicator of response to molecular targeted therapies with c-erbB inhibitors.
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PMID:Simultaneous expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 receptors in non-small-cell lung carcinomas: correlation with clinical outcome. 1744 48

Studies support involvement of the erbB/HER (human epidermal growth factor receptor) family, comprising the c-erbB-1/2/3/4 receptor proteins, in the tumourigenesis of human gliomas, raising their potential role in diagnostic and therapeutic approaches to these tumours. Reliable detection systems for these molecules in glioma tissue are therefore needed. Formalin-fixed and paraffin-embedded sections from twenty-one human glioblastomas were investigated by standard immunohistochemical procedures for expression of c-erbB-1/2/3/4 receptor proteins using commercial antibodies. All the antibodies used worked satisfactorily on paraffin-sections. For EGFR (epidermal growth factor receptor) two antibodies reactive against the external and internal domain were used. The first revealed positive immunoreactivity in 13 of 21 tumours (62 %), whereas all were positive with the latter. All glioblastomas were negative for the mutated variant of EGFR (i.e. EGFRvIII). Nine of 21 tumours (43 %) were immunoreactive for c-erbB-2, 19 of 20 tumours (95 %) for c-erbB-3, and 21 of 21 for c-erbB-4. Kaplan-Meier plots as a function of growth factor receptor expression did not show any significant association with survival among the glioblastoma patients. In conclusion, immunohistochemistry is well suited for detection of erb receptor proteins in glioblastoma tissue and demonstrated abundant and simultaneous immunoreactivity of these receptors.
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PMID:Coexpression of c-erbB 1-4 receptor proteins in human glioblastomas. An immunohistochemical study. 1798 95

The aim of our study was to describe the expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 in endometrial cancer tissue and its correlation with clinicopathologic features and prognosis of the patients. One hundred and six cases of endometrial cancer were identified from the archives of the Department of Obstetrics and Gynecology of the University of Patras. Tissue specimens from endometrial lesions were immunostained for c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4. Statistical analyses were performed using the chi square test, Kaplan-Meier method and Cox analysis. We found a significant association between c-erbB-1 expression and patient survival. A reverse correlation was found between tumor grade and c-erbB-1 expression. Tumor grade was not significantly correlated with the expression of the remaining three receptors. Stage of the tumor showed no relationship with the expression of these receptors. The ability to predict increased risks of advanced disease, recurrence, and death from abnormal molecular markers detected in curettage or endometrial biopsy specimens will facilitate pretreatment referral of these patients to gynecologic oncologists for definitive surgical treatment.
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PMID:Expression of the epidermal growth factor system in endometrial cancer. 1905 10

Amplification or overexpression of the c-erbB-2 oncogene (also known as HER-2, neu) is a frequent event in many types of human cancer including 20-30% of ovarian cancers where it characterizes a group of patients with poor prognosis (1,2). The expression of p185 (c-erbB-2) is in contrast quite restricted in normal adult tissues (3). The c-erbB-2 oncogene product (p185c-erbB-2) is a growth factor receptor (GFR) with extensive homology to the receptor for the epidermal growth factor (EGFR) and the c-erbB-3 and c-erbB-4 gene products (4). According to the hypothesis that c-erbB-2 is involved in pathogenesis and progression of human cancer, the overexpression in fibroblasts leads to the appearance of a transformed phenotype, capable of forming colonies in soft agar and inducing tumors in mice (5).
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PMID:c-erbB-2 Antisense Oligonucleotides Inhibit Serum-Induced Cell Spreading of Ovarian Cancer Cells. 2134 Aug 38

The goal of this study was to investigate the relationship among immunohistochemical expression of epithelial growth factor receptor (EGFR) family proteins, p21, p27 and prognosis in patients with high-grade astrocytoma. Expression of EGFR family proteins (c-erbB-1, c-erbB-2, c-erbB-3, c-erbB-4), p21 and p27 and Ki-67 labeling index (LI) were studied in 59 samples of high-grade astrocytoma. Expression of protein levels was analyzed by immunohistochemical staining of formalin-fixed and paraffin-embedded sections. Results were analyzed in relation to age, gender and survival. Overexpression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 was found in 40 (67.8%), 17 (28.8%), 3 (5.1%) and 42 (75.0%) samples, respectively. Similarly, low expression of p21 and p27 was observed in 50 (84.8%) and 27 (45.8%) samples. Mean Ki-67 LI was 17.3 +/- 1.1. Cox multiple regression analysis showed that c-erbB-1 (Hazard rate(HR) 1.57, 95% Confidence interval (CI) 1.08-2.36; p = 0.017), c-erbB-4 (HR 1.79, 95% CI 1.20-2.74; p = 0.004) and p27 (HR 0.50, 95% CI 0.30-0.82; p = 0.006) were significantly associated with survival. High expression of c-erbB-1 and c-erbB-4 and low expression of p27 were associated with poor prognosis in these patients.
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PMID:Prognostic significance of expression patterns of EGFR family, p21 and p27 in high-grade astrocytoma. 2136 Oct 82


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