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 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

The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all meningiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.
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PMID:Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas. 790 70

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene amplification was simultaneously determined. In a "training-set" of 313 patients, "high" TCD was associated with significantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node-positive group, high TCD level was associated with HER-2/neu amplification. After a median follow-up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node-positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node-positive patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD may act in combination with HER-2/neu amplification to promote dissemination of metastases.
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PMID:The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group. 826 79

HER-2/neu oncogene amplification or overexpression has generated considerable interest in predicting the outcome of breast cancer in Caucasians. In the present study, Northern blot analysis was used to investigate 44 primary breast cancers of different stages in Chinese patients. Nineteen tumors (43.2%) demonstrated more than two-fold expression of HER-2/neu mRNA over adjacent non-tumor breast tissue. The incidence of HER-2/neu overexpression in this series is higher than those reported in Caucasian studies. Ethnic variation is perhaps the only contributing factor. In node-negative patients, the incidence of HER-2/neu overexpression was also higher (33.3%), which could imply a worse prognosis in node-negative Chinese patients than in their Caucasian counterparts. A significant correlation between HER-2/neu overexpression and cancer stage was demonstrated. There were also trend relationships between HER-2/neu overexpression and other prognostic factors, including the number of positive axillary lymph nodes, tumor size, hormone receptor status and age at diagnosis, but none of these correlations were statistically significant. In axillary lymph node-negative patients, HER-2/neu overexpression was associated with estrogen receptor-negative status, a factor predicting worse outcome. These findings imply that HER-2/neu overexpression may identify a subgroup of node-negative patients with a poor prognosis who would otherwise have a favorable prognosis.
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PMID:HER-2/neu overexpression in Chinese breast cancers: correlation with other prognostic factors. 852 72

The administration of neoadjuvant chemotherapy to breast cancer (BC) patients with operable disease allowed studies aimed of exploring the interaction between cytotoxic treatment and tumour biology in vivo. 99 patients with T2-4, NO-1, M0 primary BC received a median of 3 cycles of either CMF regimen (cyclophosphamide, methotrexate, 5-fluorouracil) or single agent epirubicin. Endocrine therapy was also concomitantly administered in the first 45 patients with estrogen receptor positive (ER+) BC. 92 ended the treatment plan. Ki67 labelling index, estrogen receptor (ER), progesterone receptor (PgR), and c-erbB-2 oncoprotein expression were evaluated immunohistochemically in tumour biopsies obtained before and after chemotherapy. At post-chemotherapy evaluation, tumour shrinkage greater than 50% was obtained in 71 patients (79.7%), 27 of them being complete responders (30.3%). The median Ki67 labelling index, which was 13% in the first biopsy, decreased to 4.5% (p < 0.001) upon mastectomy. No significant differences were observed in steroid hormone receptor and c-erbB-2 expression before and after neoadjuvant treatment. In conclusion, neoadjuvant chemotherapy, whether associated or not to endocrine therapy, leads to a significant decrease in BC proliferation without any appreciable impact on c-erbB-2 and steroid hormone receptor expression.
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PMID:Effect of neoadjuvant chemotherapy on Ki67 labelling index, c-erbB-2 expression and steroid hormone receptor status in human breast tumours. 892 Jul 76

Cyclic phosphorylation/dephosphorylation of the retinoblastoma gene product (pRB) has been found to play a central role in the progression of the normal cell cycle, through modulation of the activity of the E2F family of transcription factors. Mutations of the retinoblastoma gene have been described in a wide variety of human malignancies including carcinomas of the breast. The present investigation reports the production and application of a new monoclonal antibody in an immunohistochemical study of pRB expression in 233 primary breast carcinomas, allowing an assessment of the contribution made by this tumour suppressor gene to tumour development and progression. Overall, there was loss of pRB expression in 21 per cent of breast tumours. Although high-grade tumours were found to lack detectable pRB more frequently than low-grade tumours, the difference did not prove statistically significant. In addition, pRB immunostaining was not related significantly to relapse or survival. No significant correlations were observed between apparent loss of pRB and tumour size, parity, patient lymph-node status, p53, c-erbB-2, c-jun, EGFR or steroid hormone receptor expression. Preliminary findings, however, did suggest a relationship between pRB expression and response to endocrine therapy.
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PMID:Retinoblastoma protein in human breast carcinoma: immunohistochemical study using a new monoclonal antibody effective on routinely processed tissues. 894 17

The overexpression of two members of the erbB oncogene family-the epidermal growth factor receptor protein (EGF-R) and the HER-2/neu protein-in breast cancer has been investigated by numerous authors. Their exact role in breast cancer is still not defined. The simultaneous investigation of EGF-R and HER-2/neu in the same study population has only rarely been performed in breast cancer. Therefore, we analyzed the EGF-R and the HER-2/neu protein expression in 142 breast cancer specimens and 12 benign breast samples by immunohistochemistry. Results of the different expression analyses were compared with established clinicopathological parameters including estrogen and progesterone receptor status. In our study group EGF-R expression correlated with advanced tumor stage, axillary lymph node status and histological grade. HER-2/neu expression correlated with larger tumor size. Neither the evaluation of a single parameter of the erbB family nor the combination of both parameters showed a significant correlation with the disease-free and the overall survival of the individual patient with breast cancer. Only the expression of the progesterone receptor correlated with a better overall survival. Steroid hormone receptor expression and the expression of EGF-R and HER-2/ neu seem to be two independent phenomena in our samples of breast cancer. The simultaneous evaluation of EGF-R and HER-2/neu expression did not lead to new information of prognostic relevance.
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PMID:Expression analyses of epidermal growth factor receptor and HER-2/neu: no advantage of prediction of recurrence or survival in breast cancer patients. 896 Jan 38

This retrospective case control study investigated the therametric value of the circulating c-erbB-2 gene product (Her-2, NEU) as (1) an eligibility criterion for high doses of chemotherapy and (2) response to standard adjuvant chemotherapy in node-positive breast cancer patients. Preoperative c-erbB-2 levels were measured in 211 locally advanced (> 3 nodes positive), pre- and perimenopausal breast cancer patients to determine if circulating levels of the gene product can assist in the determination of appropriate therapeutic options. 152 of 211 breast cancer patients received post-operatively a combination chemotherapy including the anthracycline analog mitoxantrone, while 59 patients were treated with conventional CMF therapy. Using 120 fmol/ml as a cut-off level, elevated c-erbB-2 values were found in 26 (12.3%) patients with locally advanced breast cancer. In univariate analysis significant survival differences were detected when c-erbB-2 'positive' patients were compared with c-erbB-2 'negative' patients. However, no significant survival differences were detected, when c-erbB-2 'positive' patients were compared according to regimen of adjuvant treatment. In multivariate analysis c-erbB-2 was an independent prognostic factor for predicting disease-free survival, but not for overall survival. High levels of c-erbB-2 were associated with low estrogen and progesterone receptor concentrations of the tumor cytosol. There was no correlation between elevated c-erbB-2 values and age, tumor size or degree of nodal involvement. c-erbB-2 was a better predictor of risk of recurrence than extent of nodal involvement or hormone receptor status.
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PMID:Influence of circulating c-erbB-2 serum protein on response to adjuvant chemotherapy in node-positive breast cancer patients. 906 2

p53 and c-erbB-2 expression, and their correlation with cell proliferation and steroid hormone receptors, were investigated in 121 carcinomas, 23 lobular in situ carcinomas (LCIS), 74 intraductal carcinomas (DCIS) and 24 minimal invasive carcinomas. DCIS were classified according to the EORTC classification. All markers were measured immunohistochemically on paraffin sections. None of the LCIS, 9 DCIS and 9 minimal invasive cancers showed nuclear positivity for p53. A strong association between histological type and p53 expression was found. Proliferation rates correlated with p53 expression. c-erbB-2 positivity was found in 1 LCIS, 27 DCIS and 12 minimal invasive cancers. There was a significant correlation between p53 expression and c-erbB-2. Both parameters were associated with high proliferation rate and negativity for steroid hormone receptor status. Nuclear pleomorphism could become a comparable prognostic marker in DCIS as it is for infiltrating carcinomas.
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PMID:p53 protein expression, cell proliferation and steroid hormone receptors in ductal and lobular in situ carcinomas of the breast. 947 Aug 56

The relationship between immunohistochemically measured membranous expression of erbB-2 oncoprotein and prognosis in breast cancer is controversial, and the relationship between cytoplasmic positivity and prognosis has been minimally investigated. The clinical course of 300 women with infiltrating breast carcinoma, whose tumors were stained for erbB-2 oncoprotein with CB-11 monoclonal antibody, was followed for 5 to 79 months (median, 41 months). Higher numbers of cancer-related deaths were observed in patients with moderate-to-strong cytoplasmic positivity (15/60, 25%) and strong membranous positivity (9/29, 31%) than in patients with negatively stained tumors (8/53, 15%) or tumors with weaker degrees of cytoplasmic or membranous positivity (rate similar to or less than negative tumors). Relapse-free survival was also significantly shorter in patients with tumors with strong membranous positivity and moderate-to-strong cytoplasmic positivity; much of the latter relationship was due to a high number of patients who had erbB-2-positive tumors and who were never disease free. A significant association between decreased relapse-free survival and moderate-to-strong cytoplasmic (but not membranous) positivity persisted even after correction for other variables associated with poor outcome (histologic grade, tumor size, lymph node involvement, and hormone receptor status). Moderate-to-strong erbB-2 oncoprotein cytoplasmic positivity, measured with CB-11 antibody, is associated with a poor prognosis and seems to have biologic significance.
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PMID:erbB-2 oncoprotein expression in breast carcinoma. Poor prognosis associated with high degree of cytoplasmic positivity using CB-11 antibody. 932


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