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)

Paraffin wax sections of 70 surgically resected colorectal adenocarcinomas were examined for the overexpression of HER2/c-erbB-2 oncoprotein using three different specific antibodies and the avidin-biotin immunoperoxidase technique. The patients included 38 men and 32 women aged between 47 and 80 years. The tumours were derived from various parts of the large intestinal tract, and represented all three stages of Dukes' classification and the three histological grades of differentiation. Many tumour sections also included adjacent normal or transitional mucosa. Eight tubular adenomas found in the colectomy specimens in association with some carcinomas were also examined. No positive membrane staining was seen in any of the 70 carcinomas, four adenomas, two hyperplastic polyps, nor in the adjacent normal or transitional mucosa. It is suggested that the overexpression of c-erbB-2 gene product is unlikely to be as common and as pronounced in colorectal adenocarcinoma as it is in ductal carcinoma of the breast.
 ...
PMID:HER2 (c-erbB-2) oncoprotein expression in colorectal adenocarcinoma: an immunohistological study using three different antibodies. 135 6

Data regarding the prognostic value of HER-2/neu protein expression in breast cancer are conflicting, perhaps because of short follow-up and technical difficulties in the determination (the admixture of benign elements with the biochemical method and the subjectivity of the immunohistochemical assessment). Therefore, using digital image processing, we compared the correlation between and the prognostic value of (a) quantitative immunohistochemical HER-2/neu protein expression and (b) clinical, morphometric, and flow-cytometric DNA ploidy features; histologic grade; and biochemically assessed estrogen receptor content. Paraffin-embedded invasive breast Pancers of 82 patients with long-term follow-up were used. None of the patients had received adjuvant systemic therapy. HER-2/neu protein expression was significantly correlated with DNA index, lymph node status, and tumor size and, in the diploid tumors, was weakly correlated with the percentage of S-phase cells. Strong HER-2/neu protein expression was associated with a worse prognosis (although not significantly, p = 0.07). No differences were detected between cancers with or without axillary lymph node metastases. In survival analysis, the Multivariate Prognostic Index and the morphometric features were much stronger prognosticators than HER-2/neu protein overexpression, which, however, had additional prognostic value to that of many of the features analyzed, especially when more than 35% HER-2/neu protein levels (relative to the high expression SKBR3 cell line) were present. Combined diploidy and HER-2/neu protein content greater than 35% occurred in a small group of patients (n = 3), all of whom died. Likewise, in tetraploid cancers a combination of S-phase cells greater than or equal to 7% and HER-2/neu protein content greater than 35% was an ominous sign. In multivariate analysis, strong HER-2/neu protein overexpression was prognostically over-shadowed by the morphometric features. Nevertheless, it is important to further analyze the intriguing possibility of identifying a subgroup of breast cancer patients with a very poor outcome merely using cytometric analysis of paraffin-embedded material of the primary tumor.
 ...
PMID:Comparative long-term prognostic value of quantitative HER-2/neu protein expression, DNA ploidy, and morphometric and clinical features in paraffin-embedded invasive breast cancer. 167 89

Abnormally expressed oncogenes are implicated in neoplastic transformation. We have investigated a series of endocrine tumours using immunocytochemistry as a first screening tool to detect oncogene expression. Paraffin sections of 44 pulmonary small cell carcinomas, 15 pulmonary atypical carcinoids, 12 bronchial carcinoids, 28 medullary thyroid carcinomas, 27 phaeochromocytomas, and 17 insulinomas were immunostained with antibodies to c-erbB-2, c-myc, L-myc, and N-myc. Diffuse immunoreactivity was detectable for c-erbB-2 in 8 out of 44 (18 per cent) pulmonary small cell carcinomas, 3 out of 15 (20 per cent) pulmonary atypical carcinoids, and 6 out of 27 (22 per cent) phaeochromocytomas; for c-myc in 18 out of 44 (41 per cent) pulmonary small cell carcinomas and 5 out of 15 (33 per cent) pulmonary atypical carcinoids; for N-myc in 6 out of 28 (21 per cent) medullary thyroid carcinomas; and for L-myc in 4 out of 27 (15 per cent) phaeochromocytomas. There was considerable intratumoral and intertumoral heterogeneity and, in each tumour group, no relationship was found between tumour pattern, mitotic index, and oncoprotein immunoreactivity. These results suggest that oncogene products are present in a proportion of endocrine tumours, and that specific oncoproteins seem to be related to tumour type but not to other histopathological findings. Thus, oncoprotein detection may be a useful tool for identifying subsets of endocrine tumours that are not otherwise recognizable morphologically.
 ...
PMID:Oncoprotein immunoreactivity in human endocrine tumours. 167 55

We studied c-erbB-2 and c-erbA-1 (ear-1) gene amplification, and c-erbB-2 protein expression in 123 primary Japanese breast cancers. c-erbB-2 amplification was found in 19 of the 123 tumors (15%), and c-erbA-1 was coamplified in 7 of the 19. The presence or absence of c-erbB-2 amplification correlated with the grade of cellular atypism (P = 0.008), or that of mitotic index (P = 0.002), but not with the histologic types. The tumor size (P = 0.04) and the lymph node status (P = 0.06) were associated, but the patients' age, the TNM stage, or the presence or absence of estrogen or progesterone receptors was not associated, with c-erbB-2 amplification. There were no differences in the histologic type, cellular atypism, mitotic index, and other disease parameters between tumors with c-erbB-2 amplification only and those with coamplification of c-erbB-2 and c-erbA-1. Paraffin sections from all 19 tumors with c-erbB-2 amplification, and those from only one of 104 tumors without the amplification were positively stained with polyclonal anti-c-erbB-2 protein antibody. Since the correlation between the amplification and the protein expression was excellent, such immunohistochemical studies may be substituted for the time-consuming DNA studies using Southern blotting.
 ...
PMID:c-erbB-2 and c-erbA-1 (ear-1) gene amplification and c-erbB-2 protein expression in Japanese breast cancers: their relationship to the histology and other disease parameters. 197 18

We investigated the expression of c-erB-2 protein in two matched groups of breast cancer patients, one with and one without relapse. 37 patients with relapse were compared with 42 patients without recurrence for time of observation, adjuvant treatment, age, menopausal status and estrogen receptor content. Paraffin-embedded sections were stained with the polyclonal antibody 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein. The staining of c-erbB-2 was measured on a scale of 0 to 3+. C-erbB-2 staining was negative in 16 (38%) patients in the relapse-free group, and in 8 (22%) of the patients with metastases. Neither disease-free survival (DFS) nor overall survival (OS) were dependent upon the extent of c-erbB-2 expression. An analysis by estrogen receptor (ER) status (i.e. positive or negative) and by c-erbB-2 expression (i.e. positive or negative) revealed that patients with ER-positive primaries and negative c-erbB-2 have the longest disease-free survival (DFS) and overall survival (OS). We conclude that c-erbB-2 expression might be clinically useful only if other prognostic variables (e.g. estrogen receptor content in the tumor) are also considered.
 ...
PMID:c-erbB-2 protein expression in node negative breast cancer. 197 14

Fifty-one primary human breast tumors were analyzed for amplification of the c-erbB-2 protooncogene. Thirteen (25%) of the DNA samples contained multiple gene copies. Paraffin-embedded tumor sections, available from 47 of the cases, were stained with a c-erbB-2 specific antiserum. Eighty-three % (10 of 12) of the tumors containing amplified c-erbB-2 gene copies stained positively with the c-erbB-2 specific antiserum (P = 0.03). Thirteen tumors containing single copy c-erbB-2 sequences also stained positively with the antiserum. This suggests that mechanisms other than gene amplification may lead to elevated levels of c-erbB-2 protein. Finally, there was a statistically significant correlation between c-erbB-2 protein expression and parameters used in breast cancer prognosis. Positive staining was associated with positive nodal status of the patient (P = 0.02) and with tumors showing a poor nuclear grade (P = 0.02). This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin-embedded tumor sections may have prognostic value for the course of human breast cancer.
 ...
PMID:Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. 289 63

The c-erbB-2 (HER-2/neu) proto-oncogenes is important in oncogenesis and for determination of prognosis in a number of human malignancies. DNA (Southern) hybridization and immunoblotting (Western) techniques are most commonly utilized for determining amplification status and protein expression of this proto-oncogene, respectively. These extraction techniques are often time-consuming, costly, and subject to variability depending on the histological characteristics of the tumor. Paraffin-immunohistochemistry (P-IHC), on the other hand, is time and cost-effective. In addition, this technique may offer enhanced sensitivity and specificity over extraction techniques due to the in situ nature of analysis. In data presented here, 67 cases of human mammary carcinoma were concomitantly assessed for c-erbB-2 gene copy number and oncoprotein expression by dilutional DNA hybridization and P-IHC, respectively. In 64 (95.5%) of 67 cases, high level expression was associated with gene amplification, whereas no detectable expression was associated with a normal diploid gene copy number. In two of the three discrepant cases, P-IHC predicted amplification not corroborated by Southern analysis. In these cases, tumor mass was limited by the intraductal component of the lesion or by an abundance of stromal elements within the specimen. We conclude that P-IHC offers a favorable alternative to Southern analysis in the assessment of c-erbB-2 gene copy number of this oncoprotein in human mammary carcinoma. Furthermore, immunohistochemistry may prove superior to either extraction technique in specimens with limited tumor mass, such as biopsy materials, stroma-rich tumors, or early stage lesions such as intraductal carcinoma.
 ...
PMID:Assessment of c-erbB-2 amplification by immunohistochemistry in paraffin-embedded breast cancer. 790 29

HER-2/neu oncogene amplification and overexpression of breast cancer tissue has been correlated with poor prognosis in women with both node-positive and node-negative disease. However, several studies have not confirmed this association. Review of these studies reveals the presence of considerable methodological variability including differences in study size, follow-up time, techniques and reagents. The majority of papers with clinical follow-up information are immunohistochemical studies using archival, paraffin-embedded breast cancers, and a variety of HER-2/neu antibodies have been used in these studies. Very little information, however, is available about the ability of the antibodies to detect overexpression following tissue processing for paraffin-embedding. Therefore, a series of antibodies, reported in the literature or commercially available, were evaluated to assess their sensitivity and specificity as immunohistochemical reagents. Paraffin-embedded samples of 187 breast cancers, previously characterized as frozen specimens for HER-2/neu amplification by Southern blot and for overexpression by Northern blot, Western blot, and immunohistochemistry, were used. Two multitumor paraffin-embedded tissue blocks were prepared from the previously analyzed breast cancers as a panel of cases to test a series of previously studied and/or commercially available anti-HER-2/neu antibodies. Immunohistochemical staining results obtained with 7 polyclonal and 21 monoclonal antibodies in sections from paraffin-embedded blocks of these breast cancers were compared. The ability of these antibodies to detect overexpression was extremely variable, providing an important explantation for the variable overexpression rate reported in the literature.
 ...
PMID:Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression. 790 95

The expression of both the nuclear protein p53 tumor suppressor gene product and the transmembrane C-erbB-2 protein oncogene product (p185) correlates to risk factors and outcomes in different tumor types. Their value as prognosticators in endometrial adenocarcinoma of endometrioid type (EC) has not been determined. Paraffin sections were examined immunohistochemically to study the expression of p53 protein and p185 in 112 patients with EC. p53 protein was overaccumulated in 34% and p185 in 13% of the tumors. p53 protein correlated with mitotic count and nuclear grade. Both p53 protein and p185 correlated significantly with outcome. However, they did not correlate with each other or with architectural grade or stage (which defines a high risk group), indicating a role as adjuvant prognosticators in EC. Stage and outcome did correlate, however. Both p53 protein and p185 antibodies work well on routine, formalin-fixed, paraffin-embedded tissue and are easily used in routine diagnostic procedures.
 ...
PMID:p53 protein and c-erbB-2 protein (p185) expression in endometrial adenocarcinoma of endometrioid type. An immunohistochemical examination on paraffin sections. 791 77

Paraffin embedded tissue from 249 transitional cell bladder cancers (TCC) was stained by an antibody against c-erbB-2 oncoprotein to evaluate its overexpression. The staining results were related to histopathological features and clinical follow-up data. 99/249 (39%) of tumours were positive for c-erbB-2 oncoprotein and 31/249 (12.5%) of them showed moderate or heavy staining. c-erbB-2 overexpression was related to pelvic lymph node involvement (P = 0.0355) and distant metastasis (P = 0.0058) at the time of diagnosis, whereas no significant relationship was found between T-category and c-erbB-2 oncoprotein overexpression. Expression of c-erbB-2 was related to high WHO grade (P = 0.0033), DNA aneuploidy (P = 0.0061), high S-phase fraction (P = 0.042), and several morphometric nuclear factors (P = 0.01-0.09). All the tumours with high levels of c-erbB-2 expression were tetraploid in flow cytometry (P < 0.0001). c-erbB-2 expression predicted recurrence-free survival in superficial tumours (P = 0.057) and in survival analysis moderate or intense expression of c-erbB-2 oncoprotein was related to decreased survival probability (P = 0.27). In multivariate survival analysis overexpression of c-erbB-2 had no independent prognostic value. The results show that immunohistochemical demonstration of c-erbB-2 oncoprotein overexpression in paraffin embedded archival material has no prognostic value over already established predictors in TCC.
 ...
PMID:Expression of c-erbB-2 oncoprotein in transitional cell bladder cancer. 809


1 2 3 4 Next >>