Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structure and expression of the proto-oncogene c-erbB-2 was studied in 86 patients with transitional cell carcinoma. Initial tissue samples comprised 37 grade 1, 32 grade 2 and 13 grade 3 tumours and four cases of carcinoma in situ. At the time of this first tumour sample, amplification of the c-erbB-2 gene was demonstrated by Southern blotting in 1/37 grade 1, 5/32 grade 2 and 6/13 grade 3 tumours (0.005 less than P less than 0.01). Tumour 're-occurrences' were obtained from 23 of these patients on one or more occasions. Amplification was detected in re-occurrences from seven of these 23, none of whom showed amplification in the first tumour sample. DNA was also extracted from exfoliated cells in urine collected from five cases of carcinoma in situ and c-erbB-2 amplification was demonstrated in one of these. No gene amplification was identified in patients' lymphocytes, ten biopsies of normal urothelium and 22 various intravesical pathologies. Increased expression of c-erbB-2 mRNA correlated with amplification of the gene. In addition, raised levels of mRNA were seen in the absence of gene amplification in six tumours. Immunoblotting using the polyclonal antibody 21N, raised against the c-terminus of the c-erbB-2 protein demonstrated increased amounts of a 185 kD immunoreactive protein in tumours with increased c-erbB-2 gene copy number compared with control tissues. In some tumours with high c-erbB-2 gene copy number, a 155 kD immunoreactive protein not detected in controls was expressed at higher level than the 185 kD protein. Immunocytochemistry using a monoclonal antibody AB-3, raised against the c-terminus of the c-erbB-2 protein, showed a positive reaction in the cytoplasm and cell membrane of tumours with gene amplification and in 40% of tumours with no amplification. An association was found between c-erbB-2 amplification and over-expression and the development of tumour re-occurrences. We suggest that c-erbB-2 amplification and over-expression may provide a useful molecular marker in transitional cell carcinoma of the bladder and merits further investigation as a potential prognostic indicator.
 ...
PMID:Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. 167 27

Expression of the p53, the epidermal growth factor receptor (EGFr; c-erbB-1) and c-erbB-2 proteins was studied in 82 patients with primary transitional cell carcinoma of the bladder using an immuno-histochemical method. Strong or moderate staining was found in 18% of tumours for p53 with weaker staining in a further 36% giving a total of 54% of tumours stained for p53. Strong staining was found in 15% of tumours for c-erbB-2 and in 31% for the EGFr. Tumours invading the bladder muscle were significantly more likely to be strongly stained positively for p53 and/or EGFr compared with superficial tumours: only 15% of invasive tumours were stained negatively for both p53 and EGFr. No statistical association was found between p53 and EGFr expression. Weakly positive associations were found between the expression of c-erbB-2 and p53 and between muscle invasive tumours and increased expression of c-erbB-2. Alterations in the expression of p53, c-erbB-1 and c-erbB-2 were found frequently in human transitional cell carcinoma of the urinary bladder and may be of clinical use in defining patient sub-groups of differing prognosis.
 ...
PMID:Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. 171 24

C-erbB-2 gene amplification and protein overexpression have been implicated as prognostic markers for patients with recurrent progressive bladder tumors. This event has been investigated as a potential diagnostic indicator in archival samples of transitional cell carcinoma of the bladder. Two hundred thirty-six bladder tumors from 89 patients with recurrent disease (mean follow-up, 4 years), 20 tumors from patients with no evidence of bladder tumor recurrence (mean follow-up, 7 years) and 10 normal bladder controls (patients with no history of transitional cell carcinoma) were studied. A differential PCR was used to provide a semiquantitative estimate of C-erbB-2 gene amplification. Protein overexpression was assessed immunohistochemically. Sixteen of 89 patients with recurrent disease had evidence of C-erbB-2 gene amplification. No C-erbB-2 gene amplification was seen in the nonrecurrent tumors or normal bladder controls. Of the 89 patients with recurrent bladder tumors, 43 had evidence of progressive disease, and of these, 14 patients exhibited C-erbB-2 gene amplification, indicating a strong association with gene amplification and progressive disease (P < 0.0005). Gene amplification in these patients was seen only after disease progression had occurred. Protein overexpression was seen in 50% of patients with recurrent and 45% of patients with nonrecurrent disease. No protein overexpression was seen in normal controls. Protein overexpression could not be linked to disease progression. C-erbB-2 gene amplification and protein overexpression were of predictive value in multivariate analysis for overall bladder cancer death; however stage and grade remained the most important independent prognostic variables. C-erbB-2 gene amplification and protein overexpression were of no value as independent markers for the prediction of disease recurrence or progression. It appears from these results that the role of C-erbB-2 as a diagnostic marker may far outweigh its usefulness as a prognostic indicator.
 ...
PMID:C-erbB-2 gene amplification: a molecular marker in recurrent bladder tumors? 775 96

Expression of c-erbB-2 protein, neuron-specific enolase (NSE) and DNA ploidy was studied by immunohistochemistry and flow cytometry in formalin-fixed and paraffin-embedded specimens from 104 patients with locally advanced transitional cell carcinoma of the bladder. Positive membrane bound c-erbB-2 staining was found in 15% of the tumours, and 38% of the tumours were positive for NSE. Only one tumour stained positively for both NSE and c-erbB-2. Expression of c-erbB-2 protein and NSE was neither correlated to tumour stage nor to histopathological grade. The frequency of non-diploid tumours was 78% in 49 c-erbB-2/NSE negative tumours, 98% in 40 NSE positive tumours, and 100% in 16 c-erbB-2 positive tumours (P = 0.004). Whether the c-erbB-2 expression is a useful prognostic marker in addition to other conventional parameters, remains to be shown.
 ...
PMID:Expression of c-erbB-2 protein, neuron-specific enolase and DNA flow cytometry in locally advanced transitional cell carcinoma of the urinary bladder. 809 96

Expression of the c-erbB3 protein was determined in transitional cell carcinoma of the bladder by immunohistochemistry. Strong membrane staining was observed in 10 per cent of cases (7/70) and cytoplasmic and membrane overexpression in 20 per cent (14/70). Overexpression of the epidermal growth factor (EGF) receptor (36 per cent, 25/70) and c-erbB2 proteins (9 per cent 6/70) was determined in the same series of cases. c-erbB3 overexpression was positively correlated with EGF receptor expression (P < 0.025) but appeared to be inversely associated with c-erbB2 overexpression.
 ...
PMID:Expression of the type 1 tyrosine kinase growth factor receptors EGF receptor, c-erbB2 and c-erbB3 in bladder cancer. 886 84

Bacillus Calmette Guerin (BCG) is generally regarded as an effective immunotherapy for superficially invasive papillary transitional cell carcinoma of the bladder. The exact mechanism(s) which underlie its efficacy are unknown. As C-erbB-2 oncoprotein and vascular endothelial growth factor (VEGF) have been shown to be over-expressed in TCC of the bladder, it has been postulated that they may be important in its pathogenesis. The purpose of this study was to 1.) differentially evaluate the effect of BCG immunotherapy in treated and untreated cohorts on the immunohistochemical expression of C-erbB-2 and VEGF in formalin-fixed paraffin-embedded sections of superficial and superficially invasive (Stage Ta-T1) transitional cell carcinoma of the bladder. Immunolabeling intensity was assessed independently by two pathologists and reported as a mean labeling index. The results confirm previous studies that 1.) both c-erbB-2 and VEGF are over-expressed in these tumors MLI = 90.1 and 45.7 respectively, 2.) that VEGF is an early and sensitive indicator of TCC, and 3.) that BCG has a salutary effect on papillary TCC, 66% vs. 89% recurrence rate, P = .04. Our findings show that 1.) C-erbB-2 expression is decreased in patients tumors which show response to BCG (45.7 to 38.5), P = 0.15, 2.) that BCG administration has no effect on the expression of VEGF. While the decrement in c-erbB-2 immunostaining observed in those patients who received BCG contrasts with the increase in c-erbB-2 immunolabeling observed in patients who did not receive BCG, the differences were not statistically significant and could reflect tumor grade or stage regression associated with BCG therapy. However, this study suggests that BCG differentially influences the expression of C-erbB-2 and VEGF.
 ...
PMID:Differential C-erbB-2 and VEGF expression following BCG immunotherapy in superficial papillary transitional cell carcinoma of the bladder. 1247 25

Transitional cell carcinoma of the bladder is a common tumor. While most patients presenting superficial disease can be expected to do well following treatment, still many patients will return to our office with muscle invasive and metastatic disease. Survival in advanced bladder cancer is less than 50%. Tumors of similar histologic grade and stage have variable behavior, suggesting that genetic alterations must be present to explain the diverse behavior of bladder cancer. It is hoped that through the study of the subtle genetic alterations in bladder cancer, important prognostic and therapeutic targets can be exploited. Many new diagnostic tests and gene therapy approaches rely on the identification and targeting of these unique genetic alterations. A review of literature published on the molecular genetics of bladder cancer from 1970 to the present was conducted. A variety of molecular genetic alterations have been identified in bladder cancer. Oncogenes (H-ras, erbB-2, EGFR, MDM2, C-MYC, CCND1), tumor suppressor genes (p53, Rb, p21, p27/KIP1, p16, PTEN, STK15, FHIT, FEZ1/LZTS1, bc10), telomerase, and methylation have all been studied in bladder cancer. Several have proven to be potentially useful clinical targets in the prognosis and therapy of bladder cancer such as staining for p53 and gene therapy strategies such as p53 and fez1. Clinical trials targeting HER2/neu and the EGFR pathways are underway. The UroVysion bladder cancer assay relies on FISH to detect genetic alterations in this disease. Continuing identification of the molecular genetic alterations in bladder cancer will enhance future diagnostic and therapeutic approaches to bladder cancer. Capitalizing on these alterations will allow early detection, providing important prognostic information and unique targets for gene therapy and other therapeutic approaches.
 ...
PMID:Molecular genetics of bladder cancer: targets for diagnosis and therapy. 1691 24

Expression of human epidermal growth factor receptor-2 (HER-2/neu or HER-2) oncoprotein in invasive bladder cancer was examined by immunohistochemical staining in order to evaluate the potential for molecular-targeted therapy targeting HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients who were examined at Aichi Medical University Hospital and were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2 to pT4). Immunohistochemical staining using a Hercep test kit was performed to detect HER-2 expression, which was classified into four levels from 0 to 3+ by two experienced pathologists, with 2+ and 3+ determined as positive. HER-2 staining in the primary tumor was determined as 0 in 9 (22.5%) patients, 1+ in 14 (35%), 2+ in 10 (25%), and 3+ in 7 (17.5%), resulting in 17 (17/40, 42.5%) HER-2-positive patients. According to the classification of grade, one (1/3, 33.3%) grade 2 patient and 16 (16/37, 43.2%) grade 3 patients were HER-2 positive (p=0.99). According to the classification of stage, 12 (12/22, 54.5%) pT2 patients, 2 (2/13, 15.3%) pT3 patients, and 3 (3/5, 60%) pT4 patients were HER-2 positive (p=0.05). Lymph node metastasis was found in 10 patients, and 3 (3/6, 50%) pN2 patients were HER-2 positive (p=0.32). There was a statistically significant difference between patients with HER-2-positive primary tumors and those with HER-2-positive metastatic lymph nodes (p=0.02). This study suggested that 42.5% of patients with invasive bladder cancer may benefit from molecular-targeted therapy targeting HER-2, and that the efficacy of molecular-targeted therapy can be expected even for patients with lymph node metastases as long as their primary tumors are HER-2 positive.
 ...
PMID:Potential for molecular-targeted therapy targeting human epidermal growth factor receptor-2 for invasive bladder cancer. 1754 38

Analysis of HER-2/neu gene amplification by fluorescence in situ hybridization was performed in 40 patients with invasive bladder cancer in order to evaluate the potential for molecular targeted therapy of HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients seen at the Aichi Medical University Hospital from January 2001 to December 2004 and were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2-pT4). The PathVysion kit was used to evaluate the status of HER-2/neu gene amplification, and a signal ratio > or =2.0 was considered positive for HER-2/neu gene amplification. In primary foci 5 patients (12.5%) were positive for HER-2/neu gene amplification. According to the classification of grade and stage, no statistically significant difference was observed. Lymph node metastasis was found in 10 patients, and 3 patients (30%) were positive for HER-2/neu gene amplification. In the patients with HER-2/neu gene-amplified metastatic lymph nodes, primary foci were also positive for gene amplification, showing a statistically significant difference. This study indicates that 12.5% of patients with invasive bladder cancer may benefit from molecular targeted therapy of HER-2, and that molecular targeted therapy can be expected to be effective even for patients with lymph node metastases as long as their primary foci are positive for HER-2/neu gene amplification.
 ...
PMID:Potential for molecular targeted therapy of HER-2/neu for invasive bladder cancer: examination of gene amplification by fluorescence in situ hybridization. 1791 70

Analysis of HER-2/neu expression in invasive bladder carcinoma was performed in order to evaluate the potential for molecular targeted therapy targeting HER-2. The subjects were 40 patients who were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2 to pT4). A Hercep test kit was used to detect HER-2 expression, and a Path Vysion kit was used for gene amplification. On immunohistochemical (IHC) staining, the primary tumors were HER-2 positive in 17 patients (17/40, 42.5%). According to the classification of grade, one Grade 2 patient (1/3) and 16 Grade 3 patients (16/37) were positive (P=0.99). According to the classification of stage, 12 pT2 patients (12/22, 54.5%), 2 pT3 patients (2/13, 15.3%), and 3 pT4 patients (3/5, 60%) were positive (P=0.55). Lymph node metastasis was found in 10 patients, and 3 pN2 patients were HER-2 positive (3/6, 50%) (P=0.32). A statistically significant difference was observed between HER-2-positive primary tumors and metastatic lymph nodes (P=0.02). In fluorescent in situ hybridization (FISH), HER-2/neu gene amplification was detected in the primary tumors in 5 patients (5/40, 12.5%). In all these patients, IHC staining was determined as 3+. Lymph node metastasis was found in 3 pN2 patients (3/6) (P=0.32), and in these patients with HER-2/neu gene-amplified metastatic lymph nodes, the primary tumors were also positive for gene amplification (P=0.02). In these cases, IHC staining was 3+ as well. The concordance rate of IHC-positive cases with cases positive for HER-2/neu gene amplification in FISH was 12.5% (5/40), and the concordance rate of IHC 3+ and gene amplification was 71%. This result suggests that, at present, patients who may potentially benefit from molecular targeted therapy targeting HER-2/neu for invasive bladder carcinoma should be identified by gene amplification analysis using FISH in IHC 3+ patients. In addition, it suggested that efficacy of molecular targeted therapy can be expected even for patients with metastatic lymph nodes as long as the primary tumors are positive for HER-2 expression.
 ...
PMID:Potential for HER-2/neu molecular targeted therapy for invasive bladder carcinoma: comparative study of immunohistochemistry and fluorescent in situ hybridization. 1809 76


1