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)

We analyzed the alteration of int-2, c-erbB-2 and EGFR genes in 32 cases of transitional cell carcinoma of the urinary tract, 15 cases of renal cell carcinoma and 14 cases of prostatic carcinoma by Southern blot hybridization method. Three- to 12 fold amplification of int-2 gene was observed in 4 (12.5%) of 32 transitional cell carcinomas. Of these 4 cases 3 were G3 tumor with muscle invasion and the remaining was G1, pTa tumor with subsequent recurrence of multiple tumors. The other 2 cases (6.3%) with invasive transitional cell carcinoma showed amplification of c-erbB-2 gene. Neither amplification nor gross rearrangement of EGFR gene was detected in transitional cell carcinoma. On the other hand, renal cell carcinomas and prostatic carcinomas had neither amplification nor gross rearrangement of these 3 genes. These results suggest that the int-2 gene located in chromosome locus 11q13 and the c-erbB-2 gene have a specific role in carcinogenesis and in progression of transitional cell carcinoma through their gene amplifications.
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PMID:[int-2 and c-erbB-2 gene amplification in urological cancers]. 136 54

Monoclonal antibodies to the extracellular domain of the c-erbB-2 oncoprotein (p185) react with routinely processed, paraffin-embedded human tissues, and positive staining with these reagents has been shown to correlate with gene overexpression. To determine whether such antibodies would add prognostic data to the analysis of a pre-defined subset of transitional cell carcinoma (TCC) of the bladder, we studied 20 high-grade (Grade 3) TCCs from patients known to have limited disease (Jewett-Strong stages B1, B2, and C) and for whom at least 3-yr clinical follow-up was available. Data procured from this immunohistochemical analysis were compared with tumoral DNA content (determined by flow cytometry) and conventional clinicopathologic features. Overall, 13 of 20 TCC (65%) were reactive for p185-erbB-2. However, there was no apparent relationship between p185-reactivity and either DNA content, tumor stage or clinical outcome. These results suggest that c-erbB-2 expression may be augmented in localized high-grade TCC but that there is no evidence for the contention that this phenomenon has any effect on the biologic behavior of these neoplasms. The only factor that predicted a more favorable outcome was a relatively low stage at the time of diagnosis.
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PMID:c-erbB-2 (HER-2/neu) oncopeptide immunoreactivity in localized, high-grade transitional cell carcinoma of the bladder. 136 64

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.
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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.
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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

Expression of the product of the c-erbB-2 gene, a proto-oncogene related to, but distinct from c-erbB-1 encoding the epidermal growth factor receptor (EGF-R), was investigated in human urinary bladder carcinomas. In addition, levels of EGF-R and transferrin receptor were also analyzed using an immunohistochemical approach, and the results compared with histological pattern and grading, and tumor staging. Increased expression of c-erb B-2 product was found in 32% of cases (7/22), a positive reaction being observed in 60% of transitional cell carcinoma (TCC) Grade 3 lesions (3/5), 20% of Grade 2 TCCs (2/10) and 100% of adenocarcinomas (AC) (2/2), but in none of the cases of squamous cell carcinoma (SCC). Although no statistical correlation with staging was evident, TCCs or SCCs of high grade and stage often showed EGF-R-positive staining, whereas other well differentiated lesions and normal bladder epithelium were generally negative. Most cases of urinary bladder carcinoma were positive for the transferrin receptor, which was not detected in normal bladder. The results thus suggested that a positive reaction for c-erbB-2 product is correlated with TCC histological grading or AC morphology. A high intensity of EGF-R staining in human bladder carcinomas may be associated with poor differentiation and invasion, whereas transferrin receptor expression might reflect tumor growth.
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PMID:Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas. 220 26

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

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.
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PMID:C-erbB-2 gene amplification: a molecular marker in recurrent bladder tumors? 775 96

It is important to know the proliferating ability and the malignant potential of tumor tissues. We have examined the expression of PCNA/cyclin, p53 and C-erbB-2 in transitional cell carcinoma of the human urinary bladder by an immunohistochemical method, and compared the results with the histological grade, stage and survival rate. Immunohistochemical studies, using monoclonal and polyclonal antibodies, on these proteins were performed with formaline fixed-paraffin sections of tumor tissue from 40 patients with bladder cancer. Generally, a higher grade and higher stage tumors expressed PCNA/cyclin, p53 and C-erbB-2 with a greater frequency than the tumors with a lower grade and lower stage and strongly stained cases had a lower survival rate than weakly stained cases. These findings suggest that the detection of each antigen is useful for estimating the malignant potential of transitional cell carcinoma as the adjuvant studies, because of its applicability to paraffin-embedded tissue sections and its simple, rapid technique.
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PMID:[Expression of PCNA/cyclin, p53, C-erbB-2 versus histological grade in transitional cell carcinoma of urinary bladder]. 778 54

The clinical significance of c-erb B-2 expression in urinary bladder cancer remains controversial. We performed an immunohistochemical study to examine the expression of c-erb B-2 in non-neoplastic urothelium (n = 12) and transitional cell carcinoma of the urinary bladder (n = 82). c-erb B-2 protein was localized in superficial and some intermediate cells of non-neoplastic urothelium. A total of 29 out of 82 (35%) tumors were positive for c-erb B-2 over-expression. There was no significant association of c-erbB-2 expression with tumor grade (p = 0.12), stage (p = 0.93), DNA ploidy status (p = 0.56) and the sex of patients (p = 0.5). Expression of epidermal growth factor receptor and Ki-67 index was available in 33 cases. Both parameters showed no apparent association with c-erbB-2 expression (p = 0.53 and 0.58 respectively). Factors correlated with poor patient survival by univariate analysis were tumor stage (p = 0.0001), tumor grade (p = 0.001), development of second recurrence (p = 0.002) and negative expression of c-erbB-2 (p = 0.017). Important indicators associated with first recurrence were tumor stage (p = 0.028), and c-erbB-2 expression with the risk of second recurrence (p = 0.031). Multivariate survival analysis revealed that tumor stage was among the most important prognostic factors (p = 0.029), followed by tumors without c-erbB-2 expression (p = 0.031) with a median follow-up at 46 months. The age of patients and c-erbB-2 expression were significantly associated with developing second recurrence (p = 0.031 and 0.046 respectively). The results indicate that expression of c-erbB-2 is independent of the stage and grade of bladder cancer. Although c-erbB-2 status can discriminate subpopulations with a high risk of recurrence, evaluation of its expression in paraffin-embedded tumors does not indicate poor prognosis for patients with urinary bladder cancer. To address this discrepancy a better understanding of the regulatory mechanism and physiological properties of c-erbB-2 protein in urothelium is required.
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PMID:Expression of c-erbB-2 protein in normal and neoplastic urothelium: lack of adverse prognostic effect in human urinary bladder cancer. 791 94

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


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