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)

Sections of formalin-fixed, paraffin-blocked tissue from 116 primary transitional cell carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining of cell membranes, known to correlate with gene amplification, was seen in 22 (19%) of the 116, with variable staining from tumour to tumour and within tumours themselves. Consistent with its mooted value as a prognosticator in bladder cancer, the c-erbB-2 oncoprotein was detected in 13 (of 40) grade III and 9 of the 26 muscle-invasive tumours examined compared to 1 (of 25) grade I and 6 (of 66) mucosa only (pTa) lesions. These results support further examination of c-erbB-2 expression in bladder cancer.
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PMID:An immunohistological demonstration of c-erbB-2 oncoprotein expression in primary urothelial bladder cancer. 134 55

To investigate the expression of c-H-ras (p21), c-erb B1 (EGFR) and c-erb B2 (p185) gene products in human bladder cancer, immunohistochemical studies using monoclonal antibodies to these proteins were performed on formaline fixed (within 15 hours)-paraffin sections of tumor tissues from 20 patients with bladder cancer, normal appearing adjacent bladder (non-tumor) tissues from 11 of the 20 patients, and normal bladder tissues from 3 patients who died of non-cancerous diseases as control. p21 Positive staining was demonstrated in the superficial cells of urothelium in 1 of 3 controls, also in 5 of 20 tumor tissues compact cells without vacuole in cells which have an increased nuclear/cytoplasmic ratio. Seven of 11 non-tumor tissues indicated positive staining either in superficial layer only or in whole layers of urothelium, and 1 of the latter group reacted with the monoclonal antibody to human bladder cancer produced in our laboratory. EGFR was found in 5 of 20 tumor tissues and 7 of 11 non-tumor tissues, but not in controls. Most EGFR positive tissues also indicated p21 positivity except in 1 of the tumor tissues. p185 Positive staining was demonstrated in 9 of 20 tumor tissues and 5 of 11 non-tumor tissues, but not in the controls. Furthermore, 5 of 6 tumor tissues from the patients with lymph node metastasis indicated p185 positivity. These results suggest that both p21 and EGFR may have a role in transformation and that p185 has a role in the development of metastasis in some urothelial malignancies.
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PMID:[Expression of c-H-ras, c-erb B1 and c-erb B2 gene products in human bladder cancer]. 135 18

Recently, expectations have been raised that molecular biological studies of human tumours may be of value in helping to predict future clinical behaviour, in terms of therapeutic response and long-term survival. The epidermal growth factor receptor (EGFr) is a cell surface receptor for EGF and transforming growth factor-alpha which is overexpressed by a number of human tumours. This article principally reviews previous investigations of the role of the epidermal growth factor receptor in bladder cancer and examines methods of detection, the correlation between EGFr status and known prognostic indicators and the value of assessing EGFr status in predicting clinical outcome in patients with bladder cancer. Recent studies of the c-erbB-2 proto-oncogene in bladder cancer and of cell cycling using Ki-67 are included.
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PMID:Epidermal growth factor receptor and bladder cancer: a review. 135 9

Cigarette smoking and certain types of occupational exposure to arylamines appear to be the main cause of human urinary bladder cancer. Little is known of the promotion of bladder cancer in humans, although this stage has been demonstrated in rodents. Perhaps as a consequence of initiation, multifactorial alterations of cellular genes occur. These genes include the epidermal growth factor receptor gene, erbB-2, int-2, hst, and H-ras, which exert positive control over cell growth, as well as the suppressor genes Rb-1, and the gene coding for p53. Chromosomal changes such as deletions, translocations and/or amplifications related to these genes may be of significance for prognosis of this disease.
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PMID:Chemical carcinogenesis of the urinary bladder--a status report. 161 88

HER-2/neu overexpression appears to play a role in determining the malignant potential of some human cancers. To date, no urothelial malignancies appear to have been evaluated for HER-2/neu DNA amplification, mRNA expression and protein overproduction. By Southern hybridization we detected DNA amplification and a possible structural rearrangement of the HER-2/neu oncogene in one of 12 bladder tumors. A 14 kb DNA fragment in addition to the expected 12.5 Kb fragment was found. Additionally, the HER-2/neu oncogene was amplified sixfold in the tumor compared to placental DNA. Five of 14 (36%) bladder tumors overexpressed HER-2/neu mRNA three to 38-fold compared to normal urothelium. HER-2/neu overexpression occurred in superficial and invasive tumors. Immunohistochemical analysis was performed on the one tumor with DNA amplification and the 14 tumors evaluated for mRNA expression. The tumor with DNA amplification and three of the five tumors with HER-2/neu mRNA overexpression stained positively for the p185HER-2/neu protein. These findings suggest that DNA amplification occurs infrequently in bladder cancer. Thirty-six percent of bladder cancers overexpress HER-2/neu mRNA. Immunohistochemical analysis with a p185HER-2/neu polyclonal antibody, on formalin fixed, paraffin embedded tissue, was specific for HER-2/neu overexpression but not as sensitive as Northern analysis.
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PMID:DNA, RNA and immunohistochemical characterization of the HER-2/neu oncogene in transitional cell carcinoma of the bladder. 194 10

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.
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PMID:Expression of c-erbB-2 gene product in urinary bladder cancer. 198 41

Overexpression of p53 and erbB-2 was studied by immunohistochemistry in formalin-fixed tissue samples of 179 patients with transitional cell carcinoma of the urinary bladder. p53 immunostaining was strongly correlated with tumour stage (P < 0.0001). This was driven by a marked difference in p53 expression between pTa (37% positive) and pT1 (71%) tumours, while there was no difference between pT1 and pT2-4 tumours. Similarly, a strong overall association between p53 expression and grade (P < 0.0001) was driven by a marked difference between grade 1 (28%) and grade 2 tumours (71%), and there was no significant difference between grade 2 and grade 3 tumours. Surprisingly, the frequency of erbB-2 overexpression was higher in pT1 tumours (74%) than in either pTa (49%; P = 0.0265) or pT2-T4 (56%; P = 0.0645) tumours. Both p53 and erbB-2 expression was also associated with metastasis. Metastases were found in 77% of patients with p53 positive primary tumours, but in only 50% of the patients with p53 negative primary tumours (P = 0.022). Metastases were found in 66% of patients with erbB-2 positive primaries, but in only 37% of the erbB-2 negative primaries (P = 0.020). Of 32 patients with positivity for both p53 and erbB-2, 84% developed metastases, as compared to 49% of patients with positivity for either one or neither positive (P = 0.002). We conclude that both p53 and erbB-2 overexpression are associated with early invasion in bladder cancer. Furthermore, p53 and erbB-2 may be important predictors for metastasis.
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PMID:p53 and erbB-2 protein overexpression are associated with early invasion and metastasis in bladder cancer. 750 41

Fluorescence in situ hybridization (FISH) allows visualization of chromosomes and genes in interphase nuclei. Dual labeling FISH with probes for a gene of interest and the corresponding centromere can be used to determine chromosomal deletion and gene amplification. In case of a deletion less gene signals than centromere signals are found. In case of amplification gene signal number is distinctly increased as compared to centromere signals. To study gene amplification in fresh and formalin fixed bladder cancer we used gene specific probes for erbB-2, EGF-r, and 11q13 (bcl-1, PRAD1) together with their corresponding centromere probes p17H8, p7alphaTET and plC11A. Amplification was seen in 10/140 tumors for erbB-2, in 5/107 tumors for EGF-r, and in 15/137 tumors for 11q13. Different patterns of amplification suggested that FISH allows distinction of intrachromosomal (amplified genes in clusters) and extrachromosomal amplification (diffuse distribution of signals).
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PMID:[Demonstration of gene amplification in urinary bladder cancer by fluorescent in situ hybridization (FISH)]. 751 Dec 90

We have examined the selective cytotoxicity of immunoliposomes containing doxorubicin (chemoimmunoliposomes, CILs) targeting the c-erbB-2 gene product (gp185) or gp125. Anti-gp185 and anti-gp125 CILs were prepared by conjugation of doxorubicin-containing liposomes with monoclonal antibodies SER4 (IgG) and HBJ127 (IgG) respectively. Both CILs bound to human SKBr-3 breast cancer cells and MKN-7 human gastric cancer cells, which express both antigens in high density. The IC50 of anti-gp185 CILs on protein synthesis by SKBr-3 cells was respectively 2- and 25-fold lower than that of anti-gp125 CILs and unmodified liposomes. Furthermore, anti-gp185 CILs significantly inhibited neither the phytohaemagglutin response of normal lymphocytes nor protein synthesis of gp185-negative T24 bladder cancer. Quantitative analysis of cell-associated doxorubicin revealed that, compared with anti-gp125 CILs, anti-gp185 CILs required, respectively 4.5 and 4.3 times less doxorubicin association in SKBR-3 and MKN-7 cells, for 50% cytotoxicity. In addition, flow cytometric analysis showed that both SKBr-3 and MKN-7 internalised more anti-gp185 CILs and processed them more efficiently than anti-gp125 CILs. These results suggest that anti-gp185 CILs act selectively against gp185-expressing cancer cells and that gp185 is a more sensitive antigen for CIL cytotoxicity associated with endocytosis activity.
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PMID:Cytotoxicity of anti-c-erbB-2 immunoliposomes containing doxorubicin on human cancer cells. 766 78

Frequent recurrences and multicentricity of bladder cancer suggest that alterations of the urothelium distant from the tumor may be relevant to prognosis. In this study immunohistochemistry and fluorescence in situ hybridization (FISH) were used to examine expression of p53, erbB-2, and epidermal growth factor receptor (EGF-r), genomic aberrations, and tumor cell proliferation (Ki67 LI) in normal and dysplastic urothelium. Biopsy specimens examined included normal urothelium (n = 40), mild dysplasia (n = 34), moderate dysplasia (n = 18) and carcinoma in situ (CIS; n = 20). Several different oncogene expression patterns were found, only some of which were associated with dysplasia. EGF-r expression was equally frequent in normal and dysplastic urothelium and showed a strong association with Ki67 LI (P < .0001). A purely superficial erbB-2 positivity was present in both normal and dysplastic biopsies. However, diffuse erbB-2 positivity and p53 overexpression were both associated with advanced dysplasia (P < .0001 each). FISH analysis showed erbB-2 gene amplification and p53 deletions in selected CIS, as well as a marked chromosome 17 copy number heterogeneity in all six CIS examined. These findings indicate a considerable genomic instability in bladder CIS. They show that both erbB-2 and p53 are altered during malignant transformation. Detectable oncogene expression alone, however, is not diagnostic of malignancy in bladder urothelium.
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PMID:Patterns of p53, erbB-2, and EGF-r expression in premalignant lesions of the urinary bladder. 767 97


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