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)

The new histologic classification proposed by Holland et al was applied to 127 cases of mammographically-detected ductal carcinoma in situ (DCIS). The relationship between histologic types and tumor cell expression of estrogen and progesterone receptors, p53 protein, c-erbB-2 oncoprotein, and proliferative activity markers was evaluated. There were 38 (30%) well differentiated, 39 (31%) intermediately differentiated and 50 (39%) poorly differentiated DCIS. Immunohistochemistry showed that 81% of the tumors were estrogen-receptor positive and 73% progesterone receptor positive. p53 protein and c-erbB-2 oncoprotein expression was identified in 40% and 57% of the cases, respectively. Growth-fraction determination with the Ki-67 antibody showed that 52% of the tumors had high proliferative activity. A highly significant association was found between the histologic types of DCIS and p53 protein, c-erB-b2 oncoprotein, and proliferative activity marker expression: these biological markers were more frequently overexpressed in less differentiated DCIS. No significant relationship with estrogen or progesterone receptor expression was noted. A strong relationship with the amount of tumor necrosis was also found. The clinical significance of these results should, however, be determined by long-term follow-up studies of patients with DCIS.
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PMID:Mammographically-detected ductal in situ carcinoma of the breast analyzed with a new classification. A study of 127 cases: correlation with estrogen and progesterone receptors, p53 and c-erbB-2 proteins, and proliferative activity. 783 32

The prognostic significance of the three genes most frequently amplified in breast tumors was investigated by multivariate analysis in a retrospective study of 112 primary human breast cancers. These three genes, c-myc, int-2/FGF3 (a marker for the 11q13 amplicon), and c-erbB-2/neu, were amplified in 37%, 14%, and 10% of breast tumors studied, respectively. Amplification of the c-myc gene was not related to metastasis-free survival in the total population but was a discriminant prognostic indicator in premenopausal patients. Int-2/FGF3 gene amplications were good indicators of prognosis, especially in premenopausal patients, and also in lymph-node-positive and steroid-receptor-negative patients. Int-2/FGF3 amplification and progesterone receptor status together proved to be the only independent variable predictive of metastasis-free survival. The risk of relapse in the subgroup of progesterone-receptor-negative patients was 5 times greater for those with int-2/FGF3 amplification than for those without this alteration. Amplifications at the c-erbB-2/neu locus were not significantly associated with any standard prognostic indicator or with an increased risk of recurrence. These results suggest that the combined use of classical prognostic factors and molecular markers may improve prognostic value and be applicable to patients with specific tumor phenotypes.
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PMID:Int-2/FGF3 amplification is a better independent predictor of relapse than c-myc and c-erbB-2/neu amplifications in primary human breast cancer. 789 57

The c-erbB-2 protein in breast cancer tissue extract was determined by using an enzyme-immunoassay (EIA) to see whether the quantitative determination of the oncoprotein correlates with the results of immunohistochemistry and other prognostic factors. Primary breast cancer from 104 patients was assayed for c-erbB-2 protein with an EIA that used two monoclonal antibodies directed against the extracellular domain of the protein. Pelleted tissue homogenate prepared routinely for hormone receptor assay was used as the starting material. The mean quantity of c-erbB-2 protein was 695 unit/mg protein (range 23 to 5939), and this correlated well with the results of immunohistochemical staining (P < 0.00001). It was found that 17.3% (18/104) of all tumors contained amounts of c-erbB-2 protein exceeding 1000 units/mg protein. All tumors with negative or weakly positive staining contained the oncoprotein as less than 1000 units/mg protein. The content of c-erbB-2 protein was correlated with the histologic grade (P = 0.0022), mitotic index (P = 0.0002) and degree of nuclear atypia (P = 0.013). It was inversely correlated with progesterone receptor (P = 0.006) and less strongly with estrogen receptor status (P = 0.016). Values of hormone receptor concentration and c-erbB-2 protein content showed a hyperbolic relationship that suggested biological interactions between c-erbB-2 protein and steroid hormone receptors. We conclude that c-erbB-2 protein in tissue extracts of primary breast cancer can be determined reliably by EIA, and it seems feasible to explore further the advantages of introducing EIA as a routine laboratory examination for providing additional information about the biological aspects of breast cancer.
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PMID:Determination of c-erbB-2 protein in primary breast cancer tissue extract using an enzyme immunoassay. 790 87

Previous studies have found that amplification and overexpression of the c-erbB-2 oncogene in mammary ductal adenocarcinomas predicts decreased disease-free or overall survival. Information regarding the prognostic and pathogenetic significance of oncogene amplification has been limited by difficulty obtaining sufficient quantities of high molecular weight DNA for Southern blot analysis. Differential polymerase chain reaction (PCR) has been suggested as an alternative method for evaluating gene amplification and can be performed using formalin-fixed paraffin-embedded specimens. The authors of this study used differential PCR to detect c-erbB-2 gene amplification and immunohistochemistry to evaluate c-erbB-2 expression. A highly significant degree of concordance (P < .002) between c-erbB-2 amplification and expression was observed. Abnormalities of c-erbB-2 copy number or expression were more common in tumors with higher histologic grade, and trends were noted toward association with other prognostically unfavorable biologic markers, such as reduced progesterone receptor content and DNA aneuploidy.
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PMID:Evaluation of c-erbB-2 amplification in breast carcinoma by differential polymerase chain reaction. 790 90

Concerning immunohistochemistry of the c-erbB-2 receptor in human mammary carcinoma, membranous immunostaining of tumor cells has been generally considered as a potential risk factor for early recurrence, whereas cytoplasmic reactivity has been neglected. An archival study on 463 patients with primary breast cancers demonstrates that cytoplasmic localization of p185 is significantly correlated with high estrogen and progesterone receptor levels, low histological grade and a low proliferating tumor cell fraction. In accordance with these data, patients bearing mammary carcinomas with cytoplasmic localization of p185 reactivity have a significant better overall survival than those with membranous immunostaining.
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PMID:Significance of immunohistochemical c-erbB-2 product localization pattern for prognosis of primary human breast cancer. 791 48

The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.
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PMID:C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk. 791 7

ErB-2 protein levels in breast cancer tissue extracts were determined by an enzyme immuno assay (ErbB-2 EIA "Nichirei") using anti-c-erbB-2 monoclonal antibodies, and compared with the c-erbB-2 gene amplification detected by dot blot hybridization or differential PCR, and with the overexpression detected by immunostaining. The positivities of c-erbB-2 gene amplification and overexpression in breast cancer tissues were 25.0% (14/56) and 39.3% (46/117), respectively. The cut-off values of the Erb B-2 protein in tissue extract by EIA were set at 18.0 ng/mg-protein for gene amplification and 10.4 ng/mg-protein for overexpression, respectively, from the data of breast cancer tissues which were negative for c-erbB-2 gene. The accuracy of the ErbB-2 protein levels in tissue extract with c-erbB-2 gene amplification and overexpression were 90.6% and 79.2% using these cut-off values respectively. The result of c-erbB-2 gene amplification, overexpression, and ErbB-2 protein levels were significantly correlated with negative estrogen receptor (ER) and progesterone receptor (PgR) status in tissue cytosol fraction. These results indicate that measurement of ErbB-2 protein in tissue extract is useful to estimate the c-erbB-2 gene amplification and/or overexpression in breast cancer tissues.
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PMID:[Clinical evaluation of ErbB-2 protein in tissue extract using an enzyme immuno assay (ErbB-2 EIA "Nichirei")]. 791 82

The expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R) and oncogenes c-erbB-2, c-H-ras, c-myc, as well as estrogen (ER) and progesterone (PR) receptors were studied immunohistochemically in the tissue of 21 benign and 58 malignant human breast lesions. Twenty nine (50%) of 58 carcinomas were positive for EGF-R and c-erbB-2 product, 55 (94.8%) for c-myc product, 9 (15.5%) for c-H-ras product and 17 (29%) for TGF-alpha. Eighteen of 58 (31%) carcinomas were estrogen receptor positive and 22 (38%) were positive for progesterone receptor. No correlation was found between expression of each investigated parameter and the clinical stage or degree of histological differentiation of the carcinomas. However, a significant positive correlation was observed between lymph node involvement and c-erbB-2 and EGF-R/c-erbB-2 positive tumors. A strong correlation was also observed between high levels of EGF-R and low levels of estrogen receptor. In 15 of 17 cases we found simultaneous expression of EGF-R and TGF-alpha. We also found interesting patterns in concomitant expression of the investigated parameters suggesting a possible cascade of events that occur in breast cancer cells.
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PMID:Immunohistochemical detection of TGF-alpha, EGF-R, c-erbB-2, c-H-ras, c-myc, estrogen and progesterone in benign and malignant human breast lesions: a concomitant expression. 791 21

The relative expression of estrogen receptor (ER) and progesterone receptor (PR) mRNA transcripts was measured in 71 primary breast-cancer biopsies. ER and PR binding activity were estimated in parallel by the dextran-coated-charcoal method. There was a close correlation between the amount of ER mRNA and estradiol binding activity. Tumors from post-menopausal patients contained higher levels of ER mRNA than those from pre-menopausal patients. Northern-blot analysis indicated the presence of a major band of 6.3 kb in all ER mRNA-positive tumors. Some tumors showed, in addition, 3.7- and 2.4-kb transcripts. PR binding activity and overall PR mRNA levels correlated moderately. PR mRNA and ER mRNA were associated. Four PR mRNA species with estimated sizes of 11.4, 4.5, 3.7 and 2.5 kb were detected in 14% of the PR mRNA-positive tumors. The 3.7-kb transcript was detected to varying degrees in all PR mRNA-positive biopsies, accompanied in some tumors by the 2.5-kb species. ER and PR mRNA levels > or = 50 pg/5 micrograms total RNA correlated with prolonged survival of the patients. In addition, high ER mRNA levels were associated with absence or minimal necrosis and vascular invasion together with absence or minimal level of tumor lymphocytic infiltration, but not with age, clinical stage, tumor size or overexpression of c-myc or c-erbB-2 mRNA. PR mRNA was not statistically associated with any of the above clinicopathological features. A bivariate analysis showed that both ER and PR mRNA levels were able to predict overall survival independently of the lymph-node status.
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PMID:Estrogen and progesterone receptor mRNA levels in primary breast cancer: association with patient survival and other clinical and tumor features. 792 40

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


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