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 have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express neu-related lipocalin (NRL), a member of the calycin protein superfamily. Here, we characterize the putative human homolog of NRL, neutrophil gelatinase-associated lipocalin (NGAL). ngal gene expression was found at moderate levels in only 2 of 17 human tissues examined, breast and lung. When breast cancers were examined for NGAL mRNA and protein levels, they were found to exhibit heterogeneous expression. NGAL levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma. Immuno-histochemical analysis confirmed the presence of NGAL within breast carcinoma cells but detected only low levels of this protein in normal ductal epithelium. In contrast, large amounts of the protein were localized to the lumen of normal breast ducts in the vicinity of NGAL-expressing tumors. Interestingly, unlike NRL in rat mammary carcinomas, no significant association between NGAL expression and HER-2/neu activation was found in human breast tumors. In contrast, a significant correlation between NGAL expression in breast cancer was found with several other markers of poor prognosis, including estrogen and progesterone receptor-negative status and high proliferation (S-phase fraction). NGAL levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome. No significant association between NGAL expression and disease-free or overall survival was observed.
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PMID:Heterogeneous expression of the lipocalin NGAL in primary breast cancers. 984 63

The mammary gland seems to be the only organ that is not fully developed at birth. Estrogens stimulate breast tissue via estrogen receptors (ERs). In the mammary gland, ER-mediated mechanisms have been shown to regulate: various growth factors, such as TGF-alpha and TGF-beta; enzymes, such as cathepsin D and plasminogen-activator; proto-oncogenes, such as c-fos, c-myc and HER-2/neu; cyclines and other regulatory substances that provide signaling systems for cell division and differentiation; other steroid receptors and epidermal growth factor receptors. Estrogen target genes contain estrogen-responsive elements. In these genes, transcription will be activated through interaction with the estrogen/ER protein complex. Subsequent activation of proto-oncogenes provides an explanation for the stimulating effect of estrogens on the glandular breast. Progesterone may be the key in influencing the risk of breast cancer with the peak of mitotic activity in the breast during the luteal phase of the menstrual cycle. On the other hand, in human breast cancer cell lines, both proliferation and inhibition have been observed with various progestational agents. Relevant biological and clinical issues are pregnancy and exposure to exogenous hormones. The intense hormonal stimulation of pregnancy (both estrogen and progesterone) has no adverse impact on the course of breast cancer. Pregnancy, with its mammogenetic differentiation, results in the protection of this organ from carcinogenesis. Characterization of specific lobular morphology serves as an indicator of the level of differentiation achieved by the organ, and thus provides means to assess the risk of the gland undergoing neoplastic transformation when exposed to given agents. Sufficient evidence exists to indicate the possibility of a slightly increased risk of breast cancer after approximately one decade of postmenopausal estrogen use. A review of the epidemiologic studies of postmenopausal hormone replacement and the risk of breast cancer fails to provide definitive evidence. Recent information derives from observations of cellular proliferation, plasma and tissue estradiol and progesterone receptor levels, and the percentage of apoptotic epithelial cells in human breast tissue. Several studies suggest that short-term, continuous combined HRT does not increase breast cancer recurrence or mortality. The participation of sexual hormones in the mammogenetic process during pregnancy might serve as an intermediate end point in assessing the effectiveness of hormones as chemopreventive agents. Investigations based on history, and breast morphology, should enable us to select estrogens and progestogens for HRT, and adopt optimal therapeutic regimens.
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PMID:Potential benefits of estrogens and progestogens on breast cancer. 992 May 36

The enzyme poly(A) polymerase (PAP) catalyses the polyadenylation of mRNA and its activity levels vary within the cell cycle. The levels of activity of this enzyme were measured in the cytosol of breast tumours from 62 untreated patients and compared to clinical prognostic parameters as well as other biological markers. The enzyme levels measured ranged from 3 to 46 units/mg protein. A statistically significant association was observed between high PAP activity values and the TNM stage of the disease as well as node invasiveness. Furthermore, there was a positive correlation between PAP activity values and c-erbB-2 overexpression but not with its amplification. No significant correlation was observed with c-myc amplification or overexpression and cathepsin D levels. A direct relationship between steroid receptor content and PAP activity levels, which was more prominent in the case of the progesterone receptor, was observed. However, also on the basis of previous data PAP activity may prove to be indicative of aggressive disease. Furthermore, measurements of PAP activity may contribute to the definition of the biological profile of tumour cells.
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PMID:Poly(A)polymerase activity levels in breast tumour cytosols. 1008 76

Controversy exists regarding the relationship of the degree of c-erbB-2 amplification to other prognostic factors in breast cancer. To determine the degree of amplification of c-erbB-2 exactly, a sensitive and quantitative method is required. We have developed a competitive PCR method to quantitatively determine the amplification of the c-erbB-2 oncogene. Using this method, we evaluated DNA from 27 breast cancer tissue specimens and DNA from peripheral blood leukocytes from a normal individual. Regarding the relationship between the degree of c-erbB-2 amplification and clinicopathological factors, we found a greater degree of amplification of the c-erbB-2 oncogene in estrogen receptor- negative or progesterone receptor-negative specimens than in positive ones and in lymph node metastasis-positive specimens than in negative specimens, in stages II, III, and IV of disease compared with stage I disease, and in samples with positive lymphatic vessel invasion than with no lymphatic vessel invasion. Generally, these factors were seen in the group of patients who had a bad prognosis. By univariate analysis and multivariate analysis, reverse correlation was observed between amplification of c-erbB-2 and overall survival. Regarding disease-free survival, these relationships were observed only with univariate analysis in our group of patients.
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PMID:Quantitation of c-erbB-2 gene amplification in breast cancer tissue by competitive PCR. 1021 23

Downregulation of nm-23 antimetastasis gene has been associated with disease progression in some human tumors. NPD kinase A is the product of the H1 isotype of the nm23 gene and its value as a marker of metastatic potential is well worth investigating. The expression of the nm23-H1 gene peptide was immunohistochemically evaluated in 191 primary mammary cancer tissues. A three-step immunoperoxidase staining procedure was performed and any association of our results with several classical clinicopathologic indicators, including hormonal status and c-erbB-2 oncoprotein membrane immunoexpression, was examined. NDP kinase A-positive cytoplasmic immunolabeling was noticed in 64% of all specimens (123/191) which frequently demonstrated positive progesterone receptor (PgR) status (p = 0.001) and were furthermore characterized by high PgR immunoreactivity rates. This association was significant by both univariate and multivariate statistical analysis. The double nm23-H1 (+)/PgR(+) phenotype was more frequently detected than any other combined phenotype of these markers. The nm23-H1 gene peptide was generally detected in a remarkable proportion of malignant cells, either in the invasive or the intraductal tumor components. Notably, large-cell ductal carcinomas in situ were characterized by lower nm23-H1 immunoreactivity rates when compared with other in situ cancer types. Quantitatively increased nm23-H1 immunopositive staining was more frequently observed in special histologic types of infiltrating cancers, in high nuclear grade tumors, as well as in carcinomas with high PgR levels (p = 0.05). The nm23-H1 (-)/c-erbB-2(+) phenotype was more often detected in the cancers of this study than the nm23-H1(+)/c-erbB-2(+) one. The former phenotype was correlated to postmenopausal ages as well as to extensive axillary nodal involvement by univariate statistical analysis. It is noteworthy that nm23-H1(-) status, on its own, was not statistically associated either with the presence or with a high number of involved lymph nodes. On the contrary, nm23-H1 immunopositivity was, paradoxically, more frequently observed in tumors of relatively increased TN tumor stage. Tumor progression is thus more likely to depend on the c-erbB-2 gene's overexpression. Possibly, any favorable outcome in nm23-H1(+) cases might be due to the fact that they also express PgR, which is a marker of a more functionally differentiated phenotype.
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PMID:Nm-23, c-erbB-2, and progesterone receptor expression in invasive breast cancer: correlation with clinicopathologic parameters. 1040 1

C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (>0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was similar in patients independent of plasma HER-2 levels. Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank) and OS (P = 0.003, log rank) after HDCT/ABSC. HER-2 overexpression, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression levels proved to be of independent statistical significance in predicting outcome for both PFS (P = 0.007) and OS (P = 0.002). These results suggest that overexpression of HER-2, measured by EIA in plasma may predict a shorter PFS and OS in patients with metastatic breast cancer treated with HDCT and ABSC support.
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PMID:Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support. 1046 26

We previously reported that a 660-bp sequence that is homologous to the env gene of the mouse mammary tumor virus (MMTV) but not to endogenous retroviruses or to other known genes was present in 38% of human breast cancers and in some breast cancer cell lines studied (Y. Wang et al., Cancer Res., 55: 5173-5179, 1995). Here, we have investigated whether the MMTV-like sequences were associated with the clinical, pathological, and molecular parameters that have been reported to define two subsets of human breast cancers. Archival breast carcinoma samples were analyzed for four clinical parameters, obtained from patients' records, and for six pathological characteristics. Expression of c-erbB-2, p53, bcl-2, progesterone receptor, laminin receptor, and cathepsin D was detected by immunochemistry using monoclonal antibodies. PCRs were used to amplify 250 bp of the MMTV env gene-like sequence. The chi2, log-rank, and generalized Wilcoxon tests were used to analyze the data. The MMTV env gene-like sequence was detected in 37.7% of the samples. The presence of this sequence was not significantly associated with any of the pathological clinical or biological parameters studied. It did correlate, however, with expression of the laminin receptor, a marker for invasiveness and poor prognosis. This is the first phenotypic characterization of human breast cancers containing retroviral sequences.
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PMID:Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor. 1047 94

Many different pathological and biological variables which characterize breast carcinomas have been found to be associated. The aim of this work was to analyze the complex relationship among these parameters. The pathologic, biologic, and clinical characteristics of a series of primary breast carcinomas from 676 patients were retrospectively investigated. Multiple correspondence analysis of 13 factors revealed clustering of eight pathobiologic variables, that is histologic grade, necrosis, lymphoid infiltration, number of mitoses, c-erbB-2 overexpression, p53, progesterone receptor, and bcl2 expression. An index for each tumor calculated on the basis of these eight factors served to distinguish two different tumor phenotypes, designated A and B. Phenotype A is represented by tumors sharing most of the biologic features of normal breast tissues: indeed, these tumors are characterized by a relatively high degree of differentiation, low proliferation, no necrosis or leukocyte infiltration, and no gene alterations. By contrast, phenotype B is quite divergent from the normal tissue because of its poor differentiation, high proliferation, frequent gene alterations and evidence of a host immune reaction. As regards the disease progression, these two subsets showed marked differences: phenotype A tumors had a low recurrence rate per year that remained constant over time and affected more frequently elderly patients, whereas group B tumors showed high aggressivity in the first years after surgery followed by a low long-term recurrence rate and were more frequently seen in younger patients. These data suggest that breast carcinoma consists of two different subsets that can be identified on the basis of pathobiologic features.
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PMID:Pathobiologic identification of two distinct breast carcinoma subsets with diverging clinical behaviors. 1151 69

Endometrial carcinoma is the third most common carcinoma of the female genital tract in Singapore. Although most endometrial carcinomas are detected while still at low stage, there is still a significant mortality from the disease. It is desirable that patients at high risk of relapse are identified early for consideration for additional treatment. Some information required for management can be obtained from clinical history, gross examination of the uterus and routine microscopy. These are age, stage of disease, histologic type of carcinoma (serous carcinoma and clear cell carcinomas are poor prognostic types), grade and lympho-vascular space involvement. Of less certain significance are tumour size, location and status of peritoneal cytology. Other factors currently being investigated are oestrogen and progesterone receptor status, p53 status, flow cytometric analysis for ploidy and S-phase fraction, and oncogenes such as HER-2/neu (c erbB-2). Although some of these show independent prognostic significance on multivariate analysis, it is still uncertain if the information adds significantly to the information available from routine evaluation.
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PMID:Prognostic factors in endometrial carcinoma. 1049 80

p53, c-erbB-2 protein, steroid hormone receptors, and their correlation with clinicopathologic features were investigated in 70 primary breast carcinomas. All markers were measured immunohistochemically on paraffin sections. Altered p53 expression was found in 27.1% of cases and was associated with negative estrogen receptor status. p53 immunostaining was correlated weakly with histologically lymphatic vessel invasion of carcinoma. c-erbB-2 protein overexpression was seen in 48.6% of cases. A trend was observed in the correlation between c-erbB-2 immunostaining and regional lymph node metastases. Estrogen receptor status was not associated with any histologic or clinical parameters, whereas progesterone receptor status was associated with lymph node metastasis and histologically lymphatic vessel invasion of cancer. PgR status, p53 and c-erbB-2 immunostaining may prove to be an additional criterion in histologic diagnosis of breast cancer.
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PMID:c-erbB-2, p53 protein expression and steroid hormone receptors in breast carcinomas: an immunohistochemical study. 1062 45


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