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 new monoclonal antibody to human c-jun oncoprotein, designated NCL-DK4, has been produced. NCL-DK4 has been proved to be highly effective for use on formalin-fixed, paraffin-embedded tissues, enabling the study of c-jun expression at a cellular level in both normal and neoplastic human tissues. The expression of c-jun oncogene has been examined in normal, benign, and malignant breast tissues, and c-jun-specific immunoreactivity in carcinomas has been related to histological type, tumour grade, c-erbB-2, oestrogen receptor, progesterone receptor, and epidermal growth factor receptor expression. Normal and benign breast tissues showed c-jun-specific immunostaining, which was weaker and in fewer cells compared with the c-jun immunoreactivity observed in breast carcinomas. No relationship was found between the degree of immunostaining and the extent of proliferative changes in benign breast tissues. Ninety per cent of all breast carcinomas studied showed c-jun-specific nuclear staining. There were no statistically significant differences in the intensity of c-jun immunoreactivity among grade I, II, and III infiltrating ductal carcinomas. There was no significant relationship between c-jun oncoprotein expression and c-erbB-2, oestrogen, progesterone, and epidermal growth factor receptor immunoreactivity.
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PMID:Studies of c-jun oncogene expression in human breast using a new monoclonal antibody, NCL-DK4. 793 23

The level of expression and cellular localization of the c-erbB-2 gene product in transitional cell carcinoma of the urinary tract is controversial. Analysis of the c-erbB-2 gene structure and comparison of its expression in the same cells by Southern, Northern and immunoblotting, and by immunocytochemistry minimize the errors of interpretation inherent in one technique. Such a 'correlative study' has been performed on tumours from 82 patients. c-erbB-2 gene amplification was detected in 14 per cent of initial tumours and was associated with grade (P < 0.001). Raised levels of mRNA were seen in those tumours with increased gene copy number and in 13 per cent of the remainder. Immunoblotting detected the expected 185 kD immunoreactive protein and a 155 kD protein associated with high gene copy number. Immunocytochemistry localized c-erbB-2 immunoreactivity to the cell membrane and cytoplasm, and the latter predominated. Four antibodies to c-erbB-2 (AB-3, 21N, pAb 1, and NCL CB11) were compared on contiguous sections of the same tumour and showed the same pattern of immunoreactivity. Similarly, analyses carried out in three independent laboratories identified the same cellular localization. Membrane and cytoplasmic immunoreactivity was demonstrated in all tumours with gene amplification or increased mRNA levels and in 40 per cent of the remaining tumours. We showed that immunocytochemistry requires careful standardization of techniques and quantitation between different groups. However, despite variations in the intensity of immunoreactivity, the total number of positive cells remained constant. Therefore quantitation must be based on the number of positive cells and, ideally, their immunoreactive content relative to normal and positive tissue controls.
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PMID:Immunocytochemical localization of c-erbB-2 protein in transitional cell carcinoma of the urinary bladder. 809 32

The product of c-erbB-2 gene is detected in a proportion of carcinomas from various sites and is generally associated with a high degree of malignancy. A series of 58 effusions containing malignant cells and 16 cytologically negative serous effusions was assessed by immunocytochemical methods for c-erbB-2 expression using the monoclonal antibody NCL-B11, which recognizes the internal domain of the c-erbB-2 oncoprotein. Both alcohol-fixed smears and cell blocks from formalin-fixed specimens were used. A crisp, clear cut membrane-associated positive staining was evident in 51% (30/58) malignant effusions and was restricted to metastatic adenocarcinomas. Breast and ovarian cancers showed the highest incidence of positivity. Mesotheliomas as well as non-neoplastic effusions were consistently negative. Paraffin blocks from formalin-fixed cells displayed a weak immunoreactivity when compared with their alcohol-fixed counterparts. The study shows that the c-erbB-2 oncoprotein can be easily identified in standard cytological smears: it can be of assistance in differentiating adenocarcinomas from mesotheliomas, and in selected cases it can provide a further prognostic indicator, replacing tissue immunohistochemistry.
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PMID:C-erbB-2 oncoprotein immunostaining in serous effusions. 810 24

A monoclonal antibody, NCL-CB11, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein has been used immunohistochemically in a retrospective study of formalin-fixed paraffin embedded breast neoplasm biopsies. Sixty-five out of 115 infiltrating ductal carcinoma, eleven out of 15 intraductal carcinoma and seventeen out of 22 mammary Paget's diseases exhibited positive membrane staining, indicating amplification of the gene in these tumours. In infiltrating ductal carcinoma, there was a positive correlation between c-erbB-2 overexpression and axillary lymph node metastasis as well as between the overexpression and the number of mitotic figures. These results suggest that c-erbB-2 expression might be used as a predictive marker for the worse prognosis of breast carcinoma. The significance of c-erbB-2 expression in other malignant tumours and benign lesions is also discussed.
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PMID:[Study of c-erbB-2 expression in breast neoplasms]. 810 20

An overexpression of the c-erbB-2 oncoprotein has been demonstrated in the breast cancer and has been associated with a poor prognosis. Our study involved 23 cases of mammary Paget's disease which was found to be associated with the intraductal carcinomas in 13 cases, the intraductal carcinomas supposed micro-invasive in 2 cases, the infiltrating ductal carcinomas with predominant intraductal component in 6 cases and the infiltrating ductal carcinomas in 2 cases. The presence of c-erbB-2 oncoprotein has been determined immunohistochemically with 3 different antibodies: rabbit anti-human c-erbB-2 oncoprotein A485 (Dako), c-erbB-2 oncoprotein (internal domain) mouse monoclonal antibody NCL-CB11 (Novocastra), and c-erbB-2 oncoprotein (external domain) mouse monoclonal antibody NCL-CBE1 (Novocastra). An overexpression of the c-erbB-2 oncoprotein has been observed in 21 of the 23 studied cases. We noted an intense membrane staining in the intraepidermal or intraglandular tumour cells of mammary Paget's disease. Any staining has been observed in 2 cases with glandular component of pure intraductal type. These results are identical whatever the antibody used. In a previous study concerning mammary Paget's disease, it has been noted a correlation between this overexpression and presence of large malignant cells. We also have found this notion in mammary Paget's disease where the c-erbB-2 positive neoplastic cells in the different tumour components were large with prominent cytoplasm. The obtained results argue strongly for adenocarcinomatous origin for mammary Paget's disease and exhibit that the overexpression of c-erbB-2 oncoprotein was not constantly in correlation with a poor prognosis.
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PMID:[Expression of the c-erbB-2 oncoprotein in mammary Paget's disease. Immunohistochemical study by using 3 antibodies]. 857 Feb 62

Although c-erbB-2 oncoprotein immunohistochemical expression has been thoroughly studied in a variety of human tumors, its prognostic significance remains unclear. Moreover, differences in assessment criteria further complicate the evaluation of c-erbB-2 as a prognostic marker. In the present study we examined the expression of c-erbB-2 protein in 107 patients suffering from operable (T 1,2-N0, 1 staged) non-small cell lung cancer (30 adenocarcinomas and 69 squamous cell carcinomas) treated with surgery alone. A 3-7 year of follow up (median 45 months) was available for all patients. Paraffin embedded sections were stained with the NCL-CB11 monoclonal antibody using the immunoperoxidase technique. Analysis was based on cytoplasmic reactivity as membrane staining was impossible to assess against this background. Strong positive cytoplasmic staining was identified in 20/107 (19%) of cases, weak in 30/107 (20%) and negative in 57/107 (53%). Results were correlated with patient variables (age,sex) and tumor parameters (T,N-stage, grade, histology, Ki67 proliferation index, p53 and EGFR expression). C-erbB-2 expression was not related to any of these factors. Although c-erbB-2 defined a worse prognosis, univariate analysis of survival did not confirm any statistically significant difference between the c-erbB-2 staining groups (p=0.5). T,N-stage were the only statistically significant prognostic variables. Any contribution of c-erbB-2 to the development of tumour aggressive behaviour in non-small cell lung cancer requires assessment in the specific subgroups of patients.
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PMID:C-erbB-2 oncoprotein expression in operable non-small cell lung cancer. 868 65

Twenty-four advanced (surgical stage III and IV) ovarian carcinomas and 15 borderline ovarian tumours were studied for the overexpression of nm23 and HER-2/neu (c-erb-B2) by means of immunohistochemistry on sections from routinely processed, paraffin-embedded, archival tumour blocks, using the NCL-nm23 and the NCL-CB11 monoclonal antibodies and the streptavidin-biotin-peroxidase technique. Significantly more advanced ovarian carcinomas (p = 0.034) expressed high levels of nm23 when compared to borderline tumours. HER-2/neu (c-erb-B2) expression, as could be expected, was also significantly more frequent in advanced ovarian carcinomas (p = 0.006). We were not able to find the previously reported association between nm23 and HER-2/neu overexpression in our tumours. Our results on nm23 overexpression in ovarian cancer are coincident with those previously reported using nm23-mRNA measurements on fresh ovarian tissues. Thus, ovarian carcinoma seems to belong to the group of tumours, like colon carcinoma and neuroblastoma, in which nm23 overexpression is associated with a more malignant phenotype. Immunohistochemistry performed on archival samples from ovarian carcinomas seems adequate for the demonstration of nm23 overexpression in ovarian cancer. This opens the possibility for larger studies on series of patients with a closed follow-up, which could help to establish the role of this gene in this kind of tumour.
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PMID:nm23 expression in advanced and borderline ovarian carcinoma. 870 36

It is well established that the activation of proto-oncogenes could trigger uncontrolled cell growth and cancer development. Although this correlation has already been evidenced in several human tumors, no conclusive studies have related oncogene activation with the development of prostatic neoplasia. Nevertheless, some reports suggest that c-erbB-2, which is a prognostic marker in breast cancer, could be implicated in the development of prostatic adenocarcinoma. We have studied the expression of the c-erbB-2 oncoprotein in primary prostatic tissue in a series of 70 patients with metastasic disease, by means of immunohistochemistry. The NCL-B 11 anti-c-erbB-2 monoclonal antibody was used, and the immunoreactivity was quantified by image analysis. The overall rate of prostatic-tissue sections presenting positive c-erbB-2 immunostaining was 64.3%. No significant relation was observed between histological grade and c-erbB-2 over-expression or severity of the disease, based on the extent of metastases. The average specific survival in patients with c-erbB-2 over-expression was 33 months, while it was 54 in patients with c-erbB-2 negativity; p < 0. 034. These results, as well as the logistic-regression analysis, suggest that expression of c-erbB-2 oncoprotein would be considered as an independent prognostic factor of metastatic prostate cancer. Moreover, it could discriminate between the prognosis of patients with Gleason score 2 to 7 and those with score 8 to 10. Our results suggest that the expression of c-erbB-2 oncoprotein in primary prostatic tissue could have a prognostic value in patients with metastatic prostate cancer. Int. J. Cancer (Pred. Oncol.) 84:421-425, 1999.
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PMID:Prognostic value of immunohistochemical expression of the c-erbB-2 oncoprotein in metastasic prostate cancer. 1040 97

This study investigated the degree of interlaboratory agreement when HER-2/neu was evaluated by immunohistochemistry (IHC) on archival primary breast cancer samples. IHC for HER-2/neu was performed on the same archival tissue sections from 394 invasive primary breast cancers in two different laboratories. Both laboratories used the primary antibody NCL-CB11; however, different methods of immunostaining (antigen retrieval procedure and manual processing or no antigen retrieval and autostainer processing) as well as different scoring systems were used. Fluorescence in situ hybridization (FISH), considered as the correlation method for HER-2/neu status determination, was performed using the PathVysion kit and compared to the IHC results. Forty-eight of 394 analyzed tumors (12.2%) were scored as HER-2/neu positive in one laboratory, and 109 (27.7%) in the other laboratory where antigen retrieval was performed. Complete concordance in categorization of HER-2/neu status between the two laboratories was achieved in 333 of 394 cases (84.5%). FISH performed in 248 formalin-fixed samples revealed HER-2/neu gene amplification in 55/248 (22.2%). Concordance of FISH and IHC was found in 211/248 cases (85.1%) and 220/248 cases (88.7%) when the CB11 antibody was used without and with antigen retrieval, respectively. Both IHC methods generated similar rates of false results, but with different positive predictive values. Our data demonstrate that HER-2/neu evaluation by IHC is not a reproducible technique if there is no standardization of the procedure.
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PMID:Evaluation of HER-2/NEU protein expression in breast cancer by immunohistochemistry: an interlaboratory study assessing the reproducibility of HER-2/NEU testing. 1218 71

Evaluation of gene amplification and protein expression of the c-erbB-2/neu in breast carcinomas has been an important task in breast cancer management. Although immunohistochemistry is widely applied, fluorescence in situ hybridization (FISH) technology shows its advantage in discriminating tumors in an objective manner. More recently, development of LightCycler technology permits evaluation of gene amplification with a small volume of DNA run in a 20 microL glass capillary. In this study, a series of 87 breast carcinomas were chosen for evaluation of c-erbB-2/neu gene amplification detected by both LightCycler technology and FISH. Real-time polymerase chain reaction (PCR) was performed in LightCycler capillaries with 10 ng sample DNA. By using LightCycler Relative Quantification Software version 1 (LightCycler, Roche, Mannheim, Germany), the amount of c-erbB-2 DNA was calculated as a ratio of c-erbB-2/reference gene quantity in a sample, and then the ratio was divided by the ratio of c-erbB-2 gene/reference gene quantities of a calibrator DNA (a standard DNA provided in the kit), which was run with each sample reaction in parallel. Dual-color FISH was performed on sections of the formalin-fixed, paraffin-embedded tissue array samples using the DAKO HER2 FISH pharmDX kit (DAKO A/S, Glostrup, Danmark) according to the manufacturer's instructions. Furthermore, immunohistochemistry was performed in parallel, with both the NCL-CB11 and HercepTest antibodies. Both the FISH technology and the LightCycler-PCR identified a similar percentage of tumors with c-erbB-2 gene amplification in our present study, 16% (14/87) and 15% (13/87), respectively, whereas immunohistochemistry demonstrated 32% and 34% c-erbB-2 overexpression with the NCL-CB11 and HercepTest antibodies, respectively. In addition, FISH and PCR were highly correlated in detecting tumors mainly with 3+++ c-erbB-2 protein expression by immunohistochemistry, indicating that LightCycler real-time quantification of c-erbB-2 gene may be an alternative to FISH in breast cancer clinical application.
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PMID:Real-time PCR quantification of c-erbB-2 gene is an alternative for FISH in the clinical management of breast carcinoma patients. 1549 57


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