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 expression of the 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase) gene in human breast tumors was evaluated at the level of the single cell to better understand how breast tumor cells regulate expression in response to oxidative stress. Compared to normal breast ductal cells, the level of 8-oxo-dGTPase expression in the breast tumor cells increased from non-detectable levels in normal breast to expression in 30-85% of the tumor cells in individual tumors. There was no significant association between 8-oxo-dGTPase expression and tumor grade and metastatic malignancy. The upregulation of 8-oxo-dGTPase was not directly linked to the expression of cyclins D1 and D3, estrogen receptor, p53, Ki-67 and c-erbB-2, which are genes involved in cell cycle regulation and tumor growth. The elevated expression of 8-oxo-dGTPase in human breast ductal carcinoma cells appears to be a general characteristic of breast tumors and may provide the tumor cell with a cellular defense mechanism to prevent the incorporation of 8-hydroxy-deoxyguanosine during DNA replication.
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PMID:Enhanced expression of the 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase gene in human breast tumor cells. 956 6

We examined the significance of plasma HER-2/neu as a clinical or biological marker for assessing the progression of breast cancer in African American and Hispanic women with similar socioeconomic status, similar health insurance, and similar access to health care delivery. Base line studies show the following: average age of our breast cancer patients was 48 for Hispanic and 53 for African American women. Most of our patients presented invasive ductal carcinoma, and there was no ethnic difference. A larger number of Hispanic women had stage III/IV disease at the time of diagnosis. There was no significant difference in the number of African American or Hispanic patients with ER positive or negative receptors. However, a larger number of Hispanic women had PR positive tumors, and a larger number of African American women had PR negative tumors. In general, there was no difference in the levels of HER-2/neu between the two ethnic groups. Patients with tumors >5 cm had elevated plasma HER-2/neu. However, there was no ethnic difference between tumor size and HER-2/neu levels. In addition, regional node status had no impact on plasma HER-2/neu. Patients with stage III/IV tumors had elevated plasma HER-2/neu. No ethnic difference was observed at either stage I/II or III/IV. ER positive or negative status had no significant impact on plasma HER-2/neu in either ethnic group. In contrast, PR positive patients showed elevated plasma HER-2/neu. Plasma HER-2/neu (>60 U/ml) was the strongest predictor of overall survival, visceral site metastasis, and local recurrence.
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PMID:Prognostic value of plasma HER-2/neu in African American and Hispanic women with breast cancer. 1033 53

We calculated microvessel counts (MVCs) by analyzing CD31-stained sections in three tumor zones (central, intermediate, and peripheral) in 147 cases of invasive ductal carcinoma (IDC). The purpose of the study was to discover whether there is a difference in MVC in the different zones of tumor, which zone contains the highest MVC within the tumor, from which zone the MVCs best correlate with tumor recurrence or tumor death, and which histologic factors correlate with the MVC of the tumor. Sections were scanned to assess the highest number of microvessels in any single 200 x field (0.384 mm2). In all of our cases, the average MVCs of the central, intermediate, and peripheral zones of the IDCs were 34.4, 39.4, and 51.5 per 200x field, respectively. The MVC significantly increased from the central to the peripheral zones (P < .001). In the univariate analysis, in at least one tumor zone, the MVC was correlated with T classification, tumor necrosis, fibrotic focus (a scar-like area within IDCs), and c-erbB-2 protein expression. The only factor significantly correlated with a higher MVC in all of the three zones was fibrotic focus. Moreover, in the multivariate analysis, tumors having high MVCs in the peripheral zone were significantly associated with higher hazard ratios for tumor recurrence (P < .05). This study showed that the MVC of an IDC significantly increases from the central to the peripheral zones, and it showed that angiogenesis in the peripheral zone is associated with prognosis. Therefore, estimation of angiogenesis should be performed in the peripheral zone for reliable prediction of outcome in breast cancer patients. As a surrogate for angiogenesis, fibrotic focus seems to be a useful marker for malignant potential in breast cancer.
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PMID:Optimizing microvessel counts according to tumor zone in invasive ductal carcinoma of the breast. 1034 87

Salivary duct carcinoma is a highly malignant adenocarcinoma of salivary origin. Its pathologic features are distinct from the other salivary gland tumors and bear a remarkable histologic resemblance to ductal breast carcinoma. The clinical course is rapid and the prognosis is dismal. Aggressive therapy is warranted, including primary tumor resection, cervical neck dissection, and radiotherapy. We present a case of salivary duct carcinoma of parotid origin with a very long-term evolution in clear contrast to its supposed aggressiveness. Tumor cells expressed low- and high-molecular-weight cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, and c-erbB-2 but not estrogen and progesterone receptors, actin, and S-100.
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PMID:Salivary duct carcinoma: an unusual case of long-term evolution. 1055 56

Although mucinous carcinoma (MC) of the breast is considered to originate from ductal carcinoma, it is not known whether mucinous growth begins in the intraductal carcinoma or later in the invasive carcinoma. In this study, 33 MC (16 pure without any ductal components, 10 mixed Type I with an intraductal component, seven mixed Type II with a common invasive ductal carcinoma (IDC) component)) were examined to clarify the time when mucinous growth begins. Histochemical and immunohistochemical examinations of mucin revealed that mucinous growth can begin in the intraductal carcinoma and in the common IDC. Histological transition and clonality analysis using microsatellite markers supported that some MC originate from common IDC. The pure type of MC probably originates from the intraductal carcinoma, showing a micropapillary feature. Neuroendocrine differentiation, known to be associated with MC, seemed to create the main progress in the typical MC. Moreover, we analyzed the factors of a worse prognosis of mixed MC Type II, which was strongly suggested by the lymph node status. However, no explainable differences on the cell proliferating ability, or c-erbB-2 and p53 protein overexpression were found.
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PMID:Mucinous carcinoma of the breast: a multifaceted study with special reference to histogenesis and neuroendocrine differentiation. 1059 40

Amplification and/or overexpression of HER-2/neu has been shown to be both a prognostic and predictive marker in breast cancer. Recent studies have also confirmed the efficacy of Herceptin (trastuzumab) as adjuvant therapy for patients with overexpression of HER-2/neu. Therefore, it is critical that precise and reproducible assays be used in the clinical laboratory setting for determination of the HER-2/neu status in patients with breast cancer. The objective of this study was to determine the portability (reproducibility between different institutions) of the PathVysion HER-2 fluorescence in situ hybridization (FISH) assay used for detection of amplification of the HER-2/neu gene in formalin-fixed, paraffin-embedded tissue sections of invasive ductal carcinoma of the breast. Study specimens consisted of one breast tumor with a normal HER-2/neu copy number, two tumors with a low level, and one tumor with a high level of HER-2/neu amplification. The PathVysion HER-2 assay was shown to be highly reproducible on different assay days (n = 3) and between different institutions (n = 5) in the detection of amplification of the HER-2/neu gene in routinely processed clinical specimens of breast carcinoma. In addition, this study examined the feasibility of enumerating FISH signals in 20 nuclei in contrast to 60 nuclei per specimen. Although a modest increase in variation was observed when analyzing 20 compared to 60 nuclei, the mean ratios were similar. Therefore, analysis of as few as 20 nuclei with this FISH HER-2/neu assay may be sufficient for determining the amplification level of the HER-2/neu gene.
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PMID:Fluorescence in situ hybridization (FISH) for detection of HER-2/neu amplification in breast cancer: a multicenter portability study. 1067 82

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, predisposing to the development of colorectal cancer and other tumor types such as endometrial, small bowel, stomach, ovary and urinary tract carcinoma, while most investigators find no association between HNPCC and cancer of the breast. We have identified hMLH1 mutations in 2 Amsterdam-criteria HNPCC families where both male and female gene carriers were affected with breast cancer. To investigate whether these breast cancers were caused by other genetic factors, we analyzed the 2 breast cancer susceptibility genes BRCA1 and BRCA2. In one family we did not find any mutation in the breast cancer genes, while in the other, a BRCA1 mutation segregated in the breast cancer cases. Hereditary breast cancer, and in particular BRCA1 tumors, display discrete histo-pathological and immunohistological characteristics. The tumor from a woman with both hMLH1 mutations and a BRCA1 mutation exhibited typical BRCA1 histology, e.g., grade 3 invasive ductal carcinoma with dense lymphocytic infiltration, and immunohistology, estrogen receptor (ER) negative, progesterone receptor (PgR) negative, strongly p53 positive, c-erbB-2 negative and highly Ki67 positive (>50% stained cells). The histology of the breast tumor from the man with both one hMLH1 mutation and a BRCA1 mutation was a grade 2 invasive ductal carcinoma without any special BRCA1 features. Immunohistology was also different. This might merely reflect a true difference in male breast tumor progression vs. female. We cannot exclude that the combined effect of BRCA1 and hMLH1 dysfunction has a bearing on tumor progression.
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PMID:Germline BRCA1 and HMLH1 mutations in a family with male and female breast carcinoma. 1070 98

We have examined whether the extended life span of cells induced by Bcl-2 in T(1) ductal breast carcinomas might favor the acquisition and accumulation of genetic alterations that induce lymph node metastases. We analyzed the expression of c-Myc, c-erbB-2 and epidermal growth factor receptor by immuno-histochemistry in a group of 142 T(1) (<2 cm) ductal breast carcinomas embedded in paraffin, previously studied for p53 mutation and Bcl-2 over-expression. We also measured the apoptotic status and estimated the excess risk (pOR) for lymph node metastasis according to the number of accumulated oncogene alterations and Bcl-2 and p53 expression. The linear relationship between number of oncogene alterations and presence of lymph node metastasis was statistically significant in Bcl-2-positive tumors (trend test, p = 0.03), p53-mutated tumors (trend test, p = 0.08) and tumors with loss of apoptosis (trend test, p = 0.08). Very large associations (pOR > 12) between the number of oncogene alterations and lymph node metastasis were observed among Bcl-2-positive tumors that showed increased loss of apoptosis (trend test, p = 0.03). Furthermore, in p53-negative tumors, a strong linear association was found between the number of oncogene alterations and risk of lymph node metastasis among Bcl-2-positive tumors (trend test, p = 0.03). In human T(1) ductal breast carcinoma, over-expression of Bcl-2 along with loss of apoptosis might render breast cancer cells susceptible to the acquisition of additional genetic lesions related to disease progression among p53-negative tumors. Thus, in breast cancer, there are at least 2 pathways to progression: Bcl-2- and p53-dependent mechanisms.
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PMID:Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer. 1075 91

Immunohistochemistry, DNA ploidy analysis and molecular genetics have made it possible to predict the outcome of breast cancer more precisely than routine histological examination alone. However, in routine practice, it is difficult to incorporate these methodologies in all cases. If certain histological parameters can accurately predict the outcome of patients with breast cancer, they would be more practical for routine use. We showed that the presence of fibrotic focus (FF) in invasive ductal carcinoma (IDC) is closely associated with c-erbB-2 or p53 protein expression, high proliferative activity, and high angiogenesis of the tumors. Furthermore, multivariate analyses with well-known prognostic parameters for IDC demonstrated that the presence of FF is the most useful independent parameter to predict IDC patient outcome. In addition, our data suggested that the interaction between tumor cells and stromal fibroblasts may play an important role in the formation of FF in IDC based on growth factor and growth factor receptor protein expression in the tumor cells and fibroblasts forming FF. Based on the results of our clinicopathological studies, we propose a new prognostic classification scheme for the prediction of IDC patient outcome, which consists of FF, nuclear atypia, and fat invasion. This classification has superior predicting power to existing prognostic classifications.
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PMID:New prognostic histological parameter of invasive ductal carcinoma of the breast: clinicopathological significance of fibrotic focus. 1084 11

Paraffin-embedded tissue slides from 88 infiltrating ductal breast carcinoma were examined by immunohistochemistry technique with the use of monoclonal antibody against human p65 antigen and polyclonal antibody against p65-like protein present in fetal bovine serum. Immunohistochemical analysis of expression of growth factor receptors (EGFR), protein product of oncogene c-erb B2 as well as protein product of mutated anti-oncogene p53 was also done. It was established that there is no correlation between p65 and c-erbB2, EGFR or p53 expression. In low differentiated tumors (grade III) high p53 index and high EGFR and c-erbB2 expression was connected with low p65 expression. The lack of c-erbB2 and EGFR and low p53 expression was combined usually with high p65 oncoprotein levels.
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PMID:Immunohistochemical analysis of expression of a 65 kDa oncofetal protein (p65), epidermal growth factor receptor (EGFR), oncogene c-erb B2 and tumor suppressor gene p53 protein products in breast cancer patients. 1087 Jun 81


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