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 protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c-fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell carcinomas of the lung and correlated with clinical parameters of the patients (patient survival, presence of metastases and tumor stage) and with biological characteristics of the tumors (tumor growth in nude mice, DNA-ploidy, proliferative activity, drug-resistance and P-glycoprotein or gluathione S-transferase expression). By means of immunohistochemistry, expression of c-erbB1 oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu) proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p = 0.021). In addition, these tumors were more frequently drug resistant (p = 0.0067). A significant correlation between the growth of the squamous lung carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p = 0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic factors for the aggressiveness of squamous cell carcinomas of the lung and for the response of these tumors to chemotherapy. No significant correlation was found between the expression of the c-erbB1 or c-fos gene products and stage, metastasis and DNA-ploidy. In contrast to these results, no relationship was found between c-neu or c-myc gene products expression and any of the clinical or biological parameters examined. Aneuploid squamous cell carcinomas of the lung expressed p53 more frequently than diploid tumors (p = 0.027). However, there was no significant difference between p53 expression and stage, survival of patients, metastasis, growth of the tumors in nude mice, proliferative activity and drug-resistance of the tumors.
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PMID:Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. 134 20

In order to analyze the correlation between immunohistochemical positivity for c-erbB-2 oncoprotein and prognosis in patients with malignant salivary gland tumors, 59 cases of malignant tumors of the major salivary glands, including 35 parotid gland, 20 submaxillary gland and 4 sublingual gland tumors, were studied immunohistochemically using a polyclonal antibody against c-erbB-2 oncoprotein. Positive staining was observed in 13 (22%) of the 59 cases. Interestingly, positive results were obtained only in adenocarcinoma (6/20) and carcinoma in pleomorphic adenoma (7/15), and not in any other histological types such as adenoid cystic carcinoma, mucoepidermoid tumor, and squamous cell carcinoma. There was no correlation between the degree of differentiation of adenocarcinoma and c-erbB-2 positivity. Since the carcinoma in pleomorphic adenoma positive for c-erbB-2 oncoprotein was adenocarcinoma, adenocarcinoma and adenocarcinoma in pleomorphic adenoma were placed together (n = 33), and the presence or absence of c-erbB-2 oncoprotein in this group was examined for correlation with patients' survival and other clinicopathological features, including clinical stage, tumor size, surgical margins, and lymph node status. The c-erbB-2-positive tumors tended to be more advanced and larger than negative tumors. Similarly, c-erbB-2-positive tumors were difficult to resect completely, were associated with lymph node metastasis more frequently, and showed lower disease-free survival than negative cases (P less than .05). We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands.
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PMID:Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness. 135 53

Post-recurrence survival was examined in 62 breast cancer patients who had undergone curative radical mastectomies between 1974 and 1976 and suffered recurrences within 127 months of surgery. The prognostic value of 11 clinical, histological and genetic factors, including histologic grade of malignancy and amplification of oncogenes was analyzed using univariate and multivariate analyses. Not only the site of first recurrence, clinical stage and size of primary tumor at initial surgery, and disease-free period, but also histologic grade and amplification of the c-erbB-2 proto-oncogene were significant prognostic indicators of recurrent breast cancer. Multivariate analysis using Cox's regression model, histologic grade and amplification of c-erbB-2 in the primary tumor, as well as clinical stage at surgery and site of first recurrence, were shown to be major independent prognostic factors of recurrent breast cancer. Because post-recurrence prognosis was strongly influenced by the clinical, histological and genetic status of the primary breast cancer, appropriate evaluation of the primary tumor for the grade of aggressiveness of the cancer cells, as well as the extent of cancer spread, seem to be important.
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PMID:Prognostic factors for recurrent breast cancer: univariate and multivariate analyses including histologic grade and amplification of the c-erbB-2 proto-oncogene. 135 74

In ovarian cancers, no valuable prognostic factors are available so far for predicting biological behaviour and clinical outcome. During the last years, overexpression of c-erbB-2-oncogene has been reported to be a prognostic factor in various human carcinomas. Its prognostic value in ovarian cancer is still a matter of controversy. The records and histological specimens of 243 patients with primary ovarian cancer were reviewed. Overexpression of c-erbB-2-oncogene encoded transmembrane protein p185 was determined immunohistochemically using polyclonal and monoclonal antibodies. Of 243 investigated tumours, 45 (19%) were positive. We examined the relationship between p185 and clinical stage, histological type, grading and prognosis. p185 overexpression differs within the histological subtypes of tumours. No correlation was found between p185 overexpression and stage or histological grade. The follow-up data demonstrate that patients with positive staining for p185 have a significantly worse prognosis (p = 0.001) than those with negative staining. These results suggest that overexpression of c-erbB-2 oncogene is associated with higher biological aggressiveness and unfavourable course of disease.
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PMID:[Overexpression of c-erbB-2 oncogene in primary ovarian cancers: incidence and prognostic significance in 243 patients]. 136 Apr 38

We previously reported that the expression on the primary tumour of the antigen CaMBr8 was related to a short survival, attributable either to higher tumour aggressiveness or a poor response to oophorectomy. To further verify the CaMBr8 prognostic value, we analysed retrospectively 862 breast cancer patients with a 19 year follow-up. In this series, CaMBr8 expression was found to be associated to some negative prognostic factors (premenopausal status, lymphnode invasion, a high number of mitosis and HER-2/neu oncoprotein expression), but had no influence on the patients' survival. Direct association with a poor prognosis was only evident in patients with lobular or mixed breast carcinoma, which however represent only a small fraction of the total breast cancers. Another possibility was that CaMBr8 could identify a subgroup of patients which did not respond to hormone therapy. To verify this hypothesis we evaluated on a second series of 116 patients the relationship between CaMBr8 expression and hormone-receptor levels. A negative association emerged which was also observed in vitro in the human breast cancer line MCF-7 treated with Sodium Butyrate, a differentiation inducer, which reduced hormone-receptor levels and increased CaMBr8 expression. In conclusion, the longer survival of CaMBr8 negative tumour patients observed in the initial study, was probably related to a better response to oophorectomy, due to the hormone-receptor level of their tumours.
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PMID:Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma. 155 5

p53 protein has been frequently detected at high levels in the nuclei of human breast cancer cells. We analyzed immunohistochemically the association between nuclear localization of p53 protein and clinical and histological parameters of breast cancer patients. Surgically resected tissues of 73 primary breast cancers were processed by acetone fixation and paraffin embedding and examined using an anti-p53 monoclonal antibody, PAb1801. p53 immunoreactivity was detected in the nuclei of cancer cells in 17 cases (23%). The nuclear p53 immunoreaction was closely associated with overexpression of c-erbB-2 protein (P less than 0.05), high histologic grade (P less than 0.01), advanced clinical stage (P less than 0.05), and negative estrogen receptor status (P less than 0.01). When 31 cases which had been followed up for more than 50 months were examined, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival of patients (P less than 0.01). These results suggest that immunohistochemical examination of nuclear p53 protein is clinically useful as an indicator of breast cancer aggressiveness.
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PMID:Nuclear p53 immunoreaction associated with poor prognosis of breast cancer. 167 56

The expression of ras oncogene product p21 and epidermal growth factor (EGF) receptor was studied immunohistochemically in tissues obtained from 52 patients with squamous cell carcinoma of the uterine cervix. We examined the relationship between p21 and EGF receptor expression and lymph node metastasis in cervical cancer. The data demonstrate that the patients with positive staining for ras p21 in cervical carcinomas have a higher incidence of lymph node metastasis than the patients with negative staining for p21 (P = 0.027). Although the levels of p21 expression in the metastatic sites were reduced compared to those in the primary sites, tumor cells in metastatic lymph nodes also expressed p21. No relationship was found between EGF receptor expression and lymph node metastasis. These results suggest that expression of ras oncogene product may be associated with the biological aggressiveness of cervical carcinomas.
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PMID:Expression of ras oncogene product and EGF receptor in cervical squamous cell carcinomas and its relationship to lymph node involvement. 170 25

In operable breast cancer, cell kinetics can be utilized in the prediction of the clinical outcome of patients. The discovery of monoclonal antibodies recognizing antigens related to cell proliferation has permitted the assessment of cell kinetics by rapid and practical immunocytochemical methods. It is claimed that the Ki-67 mouse monoclonal antibody recognizes an antigen expressed in proliferating cells but not present in quiescent (G0) cells. To study the relationship between Ki-67 score and DNA flow cytometric S-Phase Fraction (SPF), the latter being one of the most widely used methods to assess cell kinetics, we compared these two techniques of measurement in 122 breast carcinomas using both for each specimen. In this series 90% of tumors were Ki-67 positive, with a median value of 7.5% (range 1% to 70%). DNA flow cytometric analysis revealed that 69 tumors (57%) were aneuploid, whereas 53 were diploid. The median SPF value was 8% for diploid and 15% for aneuploid tumors (range 2% to 32%). Ki-67 scores were significantly higher in the DNA aneuploid compared to the diploid carcinomas (p = 0.015). Overall, a good correlation was found between Ki-67 and SPF values both in diploid (r = 0.60) and in aneuploid (r = 0.38) tumors. High Ki-67 scores were associated with the presence of axillary lymph node metastases (p = 0.0023) and poor histologic differentiation (p = 0.0028). Menopausal status, tumor size and peritumoral vessel invasion were unrelated to the Ki-67 score. Over-expression of the Epidermal Growth Factor receptor (EGF-r) and the c-erbB-2 oncogene were not correlated with Ki-67 staining. In conclusion, in this study Ki-67 immunostaining correlated with other indices of cell proliferation (SPF and Grade) and with some features of tumor aggressiveness (DNA aneuploidy and lymph node metastases) but seemed to be independent of some biological markers (EGR-r and c-erbB-2). Since the major objective for assessing proliferative status in Stage I-II breast carcinoma is to determine prognosis, it will have to be evaluated whether the determination of the Growth Fraction has comparable or even greater prognostic value than other cell kinetics markers.
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PMID:Breast cancer cell kinetics: immunocytochemical determination of growth fractions by monoclonal antibody Ki-67 and correlation with flow cytometric S-phase and with some features of tumor aggressiveness. 177 34

Recent work has suggested that overexpression of the HER-2/neu protooncogene may play a role in the aggressive clinical behavior of some breast tumors. Since hormones are also known to change the proliferation rate and invasiveness of these cells, we have studied the effect of sex steroid hormones and antihormones on levels of the HER-2/neu mRNA and protein in human breast cancer cell lines using complementary DNA and antibody probes. In MCF-7 cells, which contain high levels of estrogen receptor and an estradiol (E2)-inducible progesterone receptor (PR), 1 nM E2 caused a rapid drop in HER-2/neu mRNA (4.8 kilobases), to 40% of control values by 6 h, and a more gradual decrease in HER-2/neu protein, to 50% by 24 h. HER-2/neu protein and mRNA levels remained reduced throughout 1 week of E2 treatment. The effect of E2 was dose dependent, with the maximal effect seen with concentrations of 10(-10) M E2 and above, and antiestrogen partly reversed the E2-induced decrease in HER-2/neu expression. These characteristics suggest that the observed modulation of HER-2/neu is an estrogen receptor-mediated process. In contrast, progestins did not change HER-2/neu mRNA or protein levels in E2-primed MCF-7 cells that contain high levels of PR; in T47D cells, which contain low levels of ER and high levels of PR, addition of E2 or the progestin R5020 or the antiprogestin RU38,486 had no significant effect on HER-2/neu mRNA or protein levels over 6 days of treatment. These results indicate that estrogen but not progestin modulates HER-2/neu protooncogene expression in these breast cancer cell lines and suggest that aggressiveness associated with high levels of HER-2/neu mRNA and protein may be uncoupled from estrogen-stimulated proliferation in these cells.
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PMID:Hormonal modulation of HER-2/neu protooncogene messenger ribonucleic acid and p185 protein expression in human breast cancer cell lines. 197 45

c-erbB-2 Protein expression was investigated in a series of fifty primary breast cancers by means of a specific monoclonal antibody and immunocytochemistry. Specific staining was observed at the plasma membrane level of neoplastic cells, according to the reported localization of c-erbB-2 protein. Sixty-four percent of tumors scored positive, with a variable amount of stained cells. The rate of protein expression was found to exceed the reported gene amplification. No relationship was observed between c-erbB-2 protein staining and age, menopausal status or histologic subtypes. An inverse association was found between c'erbB-2 protein staining and estrogen receptor content of tumors, assayed by immunocytochemistry. A positive relationship was observed between c-erbB-2 protein expression and presence of axillary node metastasis. These findings suggest that c-erbB-2 protein expression is a marker of tumor aggressiveness and that its prognostic power deserves further investigation both in node-positive and node-negative patients.
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PMID:Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal antibody: correlation with lymph node and ER status. 197 54


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