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)

A series of 201 bladder cancer biopsy specimens was analysed immunohistochemically for the expression of pS2 protein. Altogether, 61 per cent of the tumours were pS2-negative; in 16 per cent less than 1 per cent and in 23 per cent of cases more than 1 per cent of cells were pS2-positive. Normal transitional epithelium was negative for pS2. The fraction of positive cells was higher in poorly differentiated non-papillary tumours and in invasive tumours with pelvic lymph-node (P = 0.05) and distant metastasis (P = 0.10). pS2 expression was not related to sex, while patients aged 60-70 years had low fractions of pS2-positive cells (P = 0.03). DNA ploidy, S-phase fraction, mitotic index, morphometric nuclear features, and expression of c-erbB-2, p53, and epidermal growth factor receptor were independent of expression of pS2. Tumours expressing pS2 in over 10 per cent of cells had a lower survival probability (P = 0.0486). The results show that pS2 is expressed in 40 per cent of transitional cell bladder tumours, but that this marker has no clinical significance over established prognostic factors.
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PMID:Expression of pS2 protein in transitional cell bladder tumours. 796 92

Tumor proliferation in bladder cancer is associated with tumor behavior. To assess the association between Ki-67 labeling index (LI), p53, and c-erbB-2 overexpression, formalin-fixed tissue samples of 160 patients with transitional cell carcinoma (TCC) of the urinary bladder were studied by immunohistochemistry. Ki-67 LI was strongly associated with tumor stage (P < .0001), tumor grade (P < .0001), and p53 status (P = .0014) but not with erbB-2 overexpression (P > .2). Ki-67 LI was higher in p53-positive tumors (19%) than in p53-negative tumors (14%) when all stages were compared. Ki-67 LI was independent of p53 expression in pTa tumors (p53-positive, 9%; p53-negative, 11%), showing that p53 overexpression alone is not sufficient to induce rapid tumor cell proliferation in pTa tumors. Ki-67 LI also was independent of p53 expression in pT2 to pT4 tumors (p53-positive, 20%; p53-negative, 23%), indicating that p53 expression is not necessary for rapid tumor cell proliferation in advanced stages. However, there was a striking difference in Ki-67 LI between p53-positive pT1 tumors (22.0% +/- 8.8 standard deviation [SD]; n = 20) and p53-negative pT1 tumors (9.7 +/- 8.3 SD; n = 22; P = .0001). These results suggest that increased proliferation in p53-positive pT1 tumors is caused by additional alterations that occur during tumor progression.
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PMID:p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer. 800 30

erbB-2 amplification and overexpression have been suggested as potentially useful prognostic markers in bladder cancer. We examined 141 bladder tumor specimens (45 fresh tissue samples and 96 formalin fixed tissue blocks) for erbB-2 amplification using fluorescence in situ hybridization. A dual labeling hybridization using a repetitive pericentromeric probe specific for chromosome 17 and a cosmid probe for the erbB-2 locus was performed to analyze the erbB-2 copy number in relation to chromosome 17 copy number on a cell by cell basis. Amplification (more than twice as many erbB-2 signals as centromere 17 signals per tumor) was found in 10 of 141 tumors. There was considerable heterogeneity in erbB-2 amplification. In a given tumor there was a wide range of erbB-2 copy number in amplified cells. The arrangement of erbB-2 signals in clusters in all amplified cases suggests that erbB-2 amplification occurs intrachromosomally in bladder cancer. Amplification was found only in tumors with aneusomy of chromosome 17 and was more frequent in pT2-T4 tumors than in pTa/T1 tumors. Overexpression was present without amplification in 51 tumors. All tumors with erbB-2 amplification showed erbB-2 overexpression. However, in 5 samples the proportion of cells with amplification was significantly lower than the fraction of cells with overexpression, indicating coexistence of two different mechanisms leading to overexpression in these tumors.
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PMID:Heterogeneity of erbB-2 gene amplification in bladder cancer. 809 62

Phenotypic biochemical markers of oncogenesis and differentiation were mapped in bladder biopsies to investigate changes that occur in bladder tumorigenesis and to identify markers for increased bladder cancer risk. Touch preparations from biopsy specimens from 30 patients were obtained from tumors, the adjacent bladder epithelium, and random distant bladder epithelium. Markers, including DNA ploidy, epidermal growth factor receptor (EGFR), and oncoproteins, were quantified in individual cells by using quantitative fluorescence image analysis. Cluster analysis revealed the markers fell into three independent groups: (i) G-actin and EGFR; (ii) ploidy, cytology, and p185 (HER-2/neu oncoprotein) (ERBB2); and (iii) p300, a low-grade tumor antigen. Each marker displayed a gradient of abnormality from distant field to adjacent field to tumor. Different patterns for each marker suggested a developmental sequence of bladder cancer oncogenesis; G-actin was altered in 58% of distant biopsies (vs. 0/6 normals, P < 0.001), ploidy and cytology were altered in < 20% of distant fields and approximately 80% of tumors, and the other markers were intermediate. Patterns of EGFR and p185 suggest low-and high-grade tracks diverge early (P < 0.05 by Mann-Whitney U test for EGFR and ANOVA for p185). In conclusion, this study shows that a sequence of phenotypic changes accompanies development and progression of bladder cancers. Biochemical alterations in cells of the bladder field are often detectable before abnormal pathology, and markers previously thought to be limited to tumors were found in the field. The hierarchy of expression may be useful in identifying high-risk patients, assessing completeness of response to therapy, and monitoring and predicting recurrence.
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PMID:Alterations in phenotypic biochemical markers in bladder epithelium during tumorigenesis. 836 95

To study the relationship of tumor genomic heterogeneity with bladder cancer phenotype and p53 gene alterations, 138 primary bladder tumors were examined by dual labeling fluorescence in situ hybridization (FISH) using probes for chromosome 17 centromere (p17H8) and p53 (17p13.1). The number of different aneusomic populations > 5% (and monosomic populations > 20%) of cells served as a marker for heterogeneity. Nuclear p53 overexpression and Ki67 labeling index (Ki67 LI) were determined by immunohistochemistry. The number of aneusomic populations was 0 in 53 tumors, 1 in 18, 2 in 47, 3 in 9, and > 3 in 11 tumors. Presence of aneusomy was associated with tumor grade and stage (P < 0.0001 each). Ki67 LI was low in disomic tumors (11.0 +/- 7.7), higher in tumors with 1-3 aneusomic populations (17.4 +/- 11.3), and highest in tumors with > 3 aneusomic populations (25.8 +/- 10.9; P = 0.02 for > 3 vs. 1-3 populations). Aneusomy and heterogeneity were associated with p53 alterations. Aneusomy was seen in 35% of tumors with neither p53 expression nor p53 deletion but in 97% of tumors with both p53 deletion and expression. Nine of 11 tumors with > 3 aneusomic populations exhibited both p53 deletion and overexpression. To study genomic heterogeneity in tumor progression, two recurrences and three metastases of a tumor with known erbB-2 amplification were examined for centromere 17 and erbB-2 copy number. A considerable heterogeneity in centromere 17 and erbB-2 gene copy number was found in both recurrences and metastases, indicating a marked genomic instability in these metastatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterogeneity of chromosome 17 and erbB-2 gene copy number in primary and metastatic bladder cancer. 852 69

Carcinoma of the urinary bladder is the most common malignancy in many tropical and subtropical countries and is mainly due to endemic schistosomal infection. Schistosomiasis-associated bladder cancer defines a characteristic pathology and cellular and molecular biology that differs from urothelial carcinoma of non-schistosomal origin. N-Nitroso compounds are suspected etiologic agents in the process of bladder cancer induction during schistosomiasis. Elevated levels of DNA alkylation damage have been detected in schistosome-infected bladders and are accompanied by an inefficient capacity of DNA repair mechanisms. Consequently, high frequency of G --> A transition mutations were observed in the H-ras gene and at the CpG sequences of the p53 tumor suppressor gene. Genetic changes have also been detected in the c-erbB-1 and c-erbB-2 oncogenes and in the cdkn2 and Rb tumor suppressor genes. The potential application of these mutational patterns in providing a biological marker suitable for the biomonitoring and early detection of this neoplasm could indicate new avenues of approach that might alleviate the problem in the future. It can also assist in elucidating the mechanisms by which schistosomiasis augments human bladder cancers.
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PMID:Molecular and genetic events in schistosomiasis-associated human bladder cancer: role of oncogenes and tumor suppressor genes. 869 35

We have analyzed the bladder biopsies of six bladder cancer patients exposed to high levels of 2-naphthylamine and benzidine, 11 unexposed bladder cancer patients, six subjects with benign conditions of the bladder, and 16 healthy subjects. Immunohistochemical analysis of the p21 and p185 protein products, for overexpression of ras and c-erbB-2 oncogenes, was performed. Overexpression of ras was found in four of six exposed cancer patients, 3 of 11 unexposed cancer patients, zero of six benign disease patients, and zero of 16 healthy subjects. The odds ratio for ras overexpression, comparing exposed with unexposed cases, was 5.3 (90% confidence interval 0.6 to 64). Overexpression of c-erB-2 was apparently not associated with occupational exposure.
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PMID:Exposure to aromatic amines and ras and c-erbB-2 overexpression in bladder cancer. 892 23

We investigated the expression of androgen receptor (AR) protein in transitional cell carcinoma of human urinary bladder in paraffin-embedded sections of tumours obtained from nine patients with urinary bladder cancer treated by radical cystectomy. In addition, immunoblotting of AR was also performed on selected samples. Nuclear immunoreactivity of AR was found in seven of the nine urinary bladder cancers studied. AR showed variable staining intensity within a tumour. In the immunoblots, a 110 kDa AR signal was seen with anti-AR antibody, and faint bands of 90 and 60 kDa were also observed. Immunohistochemistry of p53 and c-erbB-2 was also carried out and compared with the distribution of AR. The high frequency of AR expression suggests a role for androgens in transitional cell carcinoma of human urinary bladder.
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PMID:Immunodetection of androgen receptor in human urinary bladder cancer. 920 60

Human bladder carcinomas often express high levels of the epidermal growth factor (EGF) receptor. In three human bladder carcinoma cell lines (OBR, T24, and 647V), we show that two EGF receptor ligands, namely EGF and transforming growth factor alpha, enhanced the apoptosis due to serum starvation on cells cultured as monolayers. Conversely, EGF and transforming growth factor alpha prevented apoptosis when the same serum-starved cells were cultured as three-dimensional spheroids. Both stimulation and inhibition of apoptosis by EGF were associated with p21 WAF1/CIP1 overexpression. In 647V spheroids, EGF protection against radiation-induced apoptosis was negated by genistein and tyrphostin AG1478, suggesting that blockade of the EGF signal transduction in patients with bladder cancer may improve the radiotherapy efficacy.
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PMID:Two- and three-dimensional cell structures govern epidermal growth factor survival function in human bladder carcinoma cell lines. 926 96

Bladder cancer progression is thought to be associated with sequential genetic events. To search for the specific genetic changes associated with the metastatic process, comparative genomic hybridization was performed on 22 primary tumors and 24 metastases (10 distant and 14 nodal metastases) from 17 patients with stage pT2-4 bladder cancer. There was a striking similarity between the genetic alterations present in the primary and metastatic tumor samples from the same patient. The mean number of genetic changes/tumor was 12.2 for primary tumors and 11.7 for metastases. There was a strong concordance in the specific aberrations present in each patient's primary and metastatic lesions (mean, 75%). Concordance was also high among multiple sites from an individual primary tumor (mean, 96%) and multiple metastases from the same patient (mean, 75%). There were no specific genetic changes overrepresented in the metastases compared with their primary tumors. Genetic alterations present in more than 40% of tumors included gains on 6p, 8q, 10q, and 17q and losses involving 8p, 10q, and Y. Two regions of high-level amplification were common: (a) 10q22.1-q23.1 (32.6%); and (b) 17q11-21.3 (23.9%; the locus of erbB-2). A summary statistic was developed to quantitate the degree of clonal relationships between biopsies from the same patient. These data support a model in which minimal clonal evolution occurs in the metastatic tumor cell population after the metastatic event. When comparing primary cancers from patients with and without metastases, however, several unique genetic changes were identified in those cancers with metastases, suggesting that these loci may harbor genes important to the metastatic process.
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PMID:Genetic alterations in primary bladder cancers and their metastases. 972 60


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