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)

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

The study was carried out on 53 patients who had thyroid cancer with various degree of differentiation. We studied the expression of bcl-2, a-erbB-2, p53, and p21 ras protein. The protein encoded by bCL-2 proto-oncogene is implicated in the prolongation of cell survival by blocking programmed cell death, i.e. apoptosis. The role of p53 and bcl-2 genes in the regulation of apoptosis has important implications in oncogenesis. Wild-type p53 is thought to promote apoptosis, whilst mutant p53 has a similar effect on apoptosis as bcl-2 that is inhibition of programmed cell kinase activity. C-erb-2 protein overexpression is currently being evaluated as a potential risk factor in breast cancer patients? The ras gene family codes for a 21 kD protein (p21), which binds guanine nucleotides and possesses GTPase activity. Through this mechanism, the ras p21 protein participates in the control of cell proliferation, possibly as a signal transducer from cell surface receptors to the nucleus. Activation of ras genes has been implicated in neoplastic transformation of cells. The aim of our study is to evaluate the expression of these markers in thyroid carcinomas. All immunohistochemical study was performed in paraffin-embedded tissues pathology specimen. Any well differentiated tumor in our study was positive for bcl-2 protein. C-erb-2 immunostaining was present in tumor samples in 60% of cases. In most cases, specific membrane staining as well as a weak cytoplasmic positivity of tumor cells were seen. Immunoreactivity for p53 was positive only in 10% of cases. By immunostaining, p21 protein was expressed in 55% of the 53 tumors tested, with different degree of expression. Only some poorly differentiated tumours were positive for bcl-2, furthermore all markers tested were strongly positive in these tumours. In conclusion, our results indicate that bcl-2, c-erbB-2, p53, and p21 ras protein are differently expressed in thyroid carcinomas in relation to the degree of aggressiveness and differentiation.
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PMID:Expression of bcl-2, c-erbB-2, p53, and p21 (waf1-cip1) protein in thyroid carcinomas. 1060 83

The aggressiveness of invasive micropapillary carcinomas of the breast (MPCa) is still controversially discussed. Therefore, we investigated a total of 68 cases and studied the evolution of 54. MPCa were frequently well-differentiated cancers with the following positivities for immunohistochemistry: 74.5% estrogen receptor (ER+), 46.3% progesterone receptor (PR+), 66% Bcl2+, and 36.4% C-erbB-2+. However, in 90.5% of the cases lymph nodes were involved at diagnosis, and 70.6% of T1 tumors showed wide metastatic spread. After a mean follow-up of 52.6 months, 55.6% of the patients were disease free (DF), 7.4% had disseminated disease and 37% had died. Univariate analysis showed significant differences. Thus, the DF group of patients included 90% of those having tumors with an associated colloid pattern, 73.3% of the ER positive tumors, none of the C-erbB-2 positive tumors, and 100% of the tumors with no axillary metastasis, 77.8% of those with metastasis to up to 3 nodes, and 47.2% of those metastasizing to 4 or more nodes. However, using Cox's regression model for survival analysis, ER was the only factor associated with duration of survival (p = 0.0175). In conclusion, although long-term survival in MPCa is determined by involvement of lymph nodes, as is the case in any other breast cancer type, their short-term evolution is influenced by other factors, mostly by estrogen receptors.
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PMID:Importance of estrogen receptors for the behavior of invasive micropapillary carcinoma of the breast. Review of 68 cases with follow-up of 54. 1067 70

Primary mucinous carcinomas of the skin are very rare. To date, 120 cases have been described in the literature. This tumor is a histologic subtype of sweat gland carcinoma. Because of the histopathologic appearance, primary mucinous carcinoma of the skin can be mistaken for metastasis from extracutaneous sites. We report on the cases of two elderly women with mucinous carcinomas arising in the scalp. Immunohistochemical staining of both tumors was positive for low-molecular-weight cytokeratin and epithelial membrane antigen. Carcinoembryonic antigen was positive in Case 2. Neuroendocrine features represented by neuron-enolase-specific positivity were also observed in both cases, and Grimelius and chromogranin A positivity were observed in Case 2. In both cases, there was strong positivity for estrogen receptor and progesterone receptor. Image analysis cytometry showed a diploid DNA content with a low rate of proliferative cells and negativity for p53 and c-erbB-2 proteins in agreement with the low aggressiveness of these neoplasms.
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PMID:Primary mucinous carcinoma of the skin. 1077 Apr 39

The prognostic and predictive role of c-erbB-2 oncoprotein in human malignancies remains controversial. The pattern of expression and the biological behaviour of c-erbB-2 protein was investigated in a series of 89 locally advanced squamous carcinomas of the head and neck. Possible associations between c-erbB-2 and T,N-stage, histological grade, microvessel density and the expression of bcl-2 and p53 proteins were sought. Biopsy material had been collected prior to the initiation of treatment which consisted of platinum based induction chemotherapy or concurrent chemotherapy and radiotherapy. In all cases, follow-up of at least 2 years duration was available. Positive staining was seen in 27 out of 89 (30.4%) cases and was invariably cytoplasmic, exhibiting strong reactivity in more than 50% of tumour cells. Such c-erbB-2 overexpressing tumours were not associated with a response to radiotherapy and/or induction chemotherapy. Further, survival analysis did not disclose any difference in the overall or relapse free survival between c-erbB-2 positive and negative cases. Similarly, no relationship was found with T,N-stage, histological grade and bcl-2 or p53 expression. There was, however, a significant inverse association between c-erbB-2 expression and microvessel density (p = 0.0001). Interestingly, tumours with low vascular grade (VG; MS < 26) and positive c-erbB-2 expression were less frequently associated with local aggressiveness compared to c-erbB-2 negative tumours and low VG (5/27 vs. 12/18; p = 0.001), or to c-erbB-2 negative tumours and high VG (MS > 27) (5/27 vs. 19/44; p = 0.03). These differences were statistically significant but were not related to treatment response or prognosis. Nonetheless, when patients with highly angiogenic tumours were analysed for survival, irrespective of the c-erbB-2 status, they showed a poorer prognosis than those having a low microvessel density (p = 0.06 and 0.05 for overall and relapse free survival, respectively). Six out of 89 patients presented with distant metastases, five of which had tumours negative for c-erbB-2 expression. Our results seem to indicate that the pattern of c-erbB-2 expression in locally advanced inoperable head and neck cancer is exclusively cytoplasmic. c-erbB-2 reactivity is of little value in predicting survival or chemo-radiotherapeutic response. Expression of genes related to angiogenesis or other invasion and migration pathways are, apparently, more important.
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PMID:c-erbB-2 oncoprotein is overexpressed in poorly vascularised squamous cell carcinomas of the head and neck, but is not associated with response to cytotoxic therapy or survival. 1081 Mar 87

Young age does not seem to be directly related to the aggressiveness of the disease among patients with breast cancer. Identification and analysis of the alterations in a susceptibility gene expression in breast cancer occurring in young women may allow identification of those patients in whom tumors will show an aggressive clinical course. The purpose of the present study was to evaluate the association of BRCA1, H-ras, and c-erbB-2 gene expression with clinicopathologic parameters of prognosis in breast cancer. Formalin-fixed, paraffin-embedded tissue from 35 patients with breast cancer younger than 35 years were immunohistochemically stained for BRCA1, H-ras, and c-erbB-2 expression with monoclonal antibodies. For each antibody, immunoreactivity was assessed by a semiquantitative scoring system. Each case was also graded according to the modified Bloom-Richardson criteria and evaluated for Ki-67 labeling index, hormonal status, tumor size, distant metastasis, and axillary lymph node involvement. Strong expression of c-erbB-2 and H-ras were observed in 9 cases (25.7%) and 13 cases (37.2%), respectively. Loss of BRCA1 expression was found in five cases (14.3%). Statistical analysis showed that loss of BRCA1 expression was significantly associated with higher Ki-67 labeling index and greater tumor size. In addition, stronger H-ras expression was significantly associated with lymph node involvement and distant metastasis. However, c-erbB-2 immunoreactivity did not show statistical significance with any prognostic parameters. We conclude that, although care must be taken not to overstate the importance of our results in view of the lack of information on clinical outcome, alterations in BRCA1 and H-ras gene expression might be of prognostic importance because of the role of H-ras protein on metastatic behavior and the role of BRCA1 protein on tumor growth. However, c-erbB-2 expression seems to be of no importance in the prognosis of breast cancer occurring in young women.
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PMID:BRCA1, C-erbB-2, and H-ras gene expressions in young women with breast cancer. An immunohistochemical study. 1093 43

We measured the expression of the type I growth factor receptor gene family [epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4] in a series of 365 unselected primary breast cancers. The expression was quantified with a real-time one-step reverse transcriptase-PCR (RT-PCR) assay, based upon the 5' nuclease activity of the Taq polymerase and using an Abi Prism 7700 Sequence Detector System (Perkin-Elmer, Courtaboeuf, France). c-erbB-3 and c-erbB-4 were positively correlated to each other (Spearman test) and negatively correlated to EGFR. EGFR and c-erbB-2 were inversely correlated to the presence of estradiol receptors (ER) and progesterone receptors (PgR), and positively correlated to the histoprognostic grading (HPG). Conversely, c-erbB-3 and c-erbB-4 were positively correlated to the presence of ER and PgR, and inversely correlated to the grading HPG. EGFR was inversely related (chi2 test) to the presence of ER and PgR, and positively associated with HPG. In contrast, both c-erbB-3 and c-erbB-4 were inversely related to HPG, and positively associated with the presence of ER and PgR. The expression level of EGFR and c-erbB-2 was significantly higher in ER- and PgR-negative tumors compared with ER- and PgR-positive tumors (Student's t test), and in tumors with higher grade compared with tumors with lower grade. The expression level of c-erbB-3 and c-erbB-4 was significantly higher in ER- and PgR-positive tumors compared with ER- and PgR-negative tumors and in tumors with lower grade compared with tumors with higher grade. In overall survival studies, Cox univariate analyses showed prognostic values of EGFR [> or = median; P = 0.026; risk ratio (RR), 1.6], c-erbB-3 (> or = median; P = 0.0093; RR, 0.58), c-erbB-4 (> or = median; P = 0.0024; RR, 0.52), HPG, node involvement, tumor diameter, ER, and PgR. In Cox multivariate analyses, tumor diameter, ER, and PgR had a prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of tumor diameter, node involvement, and c-erbB-4 (P = 0.015; RR, 0.65). These three parameters maintained their prognostic value in multivariate analyses (c-erbB-4, P = 0.035; RR, 0.67). This study confirms that EGFR expression and c-erbB-2 expression are markers of tumor aggressiveness in breast cancer. Conversely, we demonstrate that c-erbB-3 and c-erbB-4 elevated expressions are associated with a better prognosis.
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PMID:Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. 1110 35

The product of the HER-2/neu proto-oncogene, HER2, is the second member of the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors and has been suggested to be a ligand orphan receptor. Ligand-dependent heterodimerization between HER2 and another HER family member, HER1, HER3 or HER4, activates the HER2 signaling pathway. The intracellular signaling pathway of HER2 is thought to involve ras-MAPK, MAPK-independent S6 kinase and phospholipase C-gamma signaling pathways. However, the biological consequences of the activation of these pathways are not yet completely known. Amplification of the HER2 gene and overexpression of the HER2 protein induces cell transformation and has been demonstrated in 10% to 40% of human breast cancer. HER2 overexpression has been suggested to associate with tumor aggressiveness, prognosis and responsiveness to hormonal and cytotoxic agents in breast cancer patients. These findings indicate that HER2 is an appropriate target for tumor-specific therapies. A number of approaches have been investigated: (1) a humanized monoclonal antibody against HER2, rhuMAbHER2 (trastuzumab), which is already approved for clinical use in the treatment of patients with metastatic breast cancer; (2) tyrosine kinase inhibitors, such as emodin, which block HER2 phosphorylation and its intracellullar signaling; (3) active immunotherapy, such as vaccination; and (4) heat shock protein (Hsp) 90-associated signal inhibitors, such as radicicol derivatives, which induce degradation of tyrosine kinase receptors, such as HER2.
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PMID:Biological and clinical significance of HER2 overexpression in breast cancer. 1118 Jul 65

The mutation of the p53 gene is a common phenomenon in numerous human tumors including breast cancer. It leads to an accumulation of nonfunctioning p53 protein in the cell nuclei, which can be detected by immunohistochemical techniques. In breast cancer overexpression of mutated p53 protein has been correlated to a poor prognosis. Our study is an immunohistochemical analysis of p53 in 82 cases of breast cancer in young (< or = 30 years old) Kuwaiti women, correlating it with histopathological grade, lymph node status, estrogen (ER) and progesterone receptor (PgR) content, tumor cell proliferation (immunostaining for Ki-67) and expression of c-erbB-2 oncoprotein. p53 immunostaining was found in 47 (57.32%) of the carcinomas. 65% of them displayed positive immunostaining for c-erbB-2. 63.7% of tumors with p53 overexpression were aneuploid. 64.8% of the p53 positive tumors were node positive. 93.5% of the p53 immunopositive carcinomas were ER-negative, and in 95.7% of this subclass of patients no PgR could be detected. The vast majority of p53 positive carcinomas were grade III (76.6%), 21.3% were grade II and 2.1% grade I, but neither tumor grade or tumor size showed a correlation with p53 expression. A significant negative correlation between ER- and PgR-content (p = 0.006) and immunostaining for p53 was observed. Our study provided evidence that the association of negative hormone receptor status and positivity for p53 immunostaining points to a greater tumor aggressiveness.
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PMID:Immunohistochemical detection of p53 protein expression in breast cancer in young Kuwaiti women. 1129 37

Our aim was to compare the prognostic value of c-erbB-2 gene amplification analyzed by Southern blot with that of protein (p185) over-expression measured by immunohistochemistry in 172 patients with operable breast cancer (BC). Amplification and p185 over-expression were found in 31 (18%) and 51 (30%) BCs, respectively. All but 1 of the tumors showed both amplification and over-expression, while 21 (12%) tumors displayed over-expression without amplification. The risk of death associated with c-erbB-2 gene amplification and p185 over-expression was evaluated by multivariate analysis, taking into account tumor size, histoprognostic grade, hormone receptors and axillary node status. During a mean follow-up of 9.5 (+/-2) years, node involvement (p < 0.001), c-erbB-2 gene amplification (p = 0.02) and negative hormone receptors (p = 0.02) were found to be independent prognostic indicators of the risk of death. Over-expression of p185 with no amplification was not correlated with this risk. When the risk of death associated with c-erbB-2 amplification was studied according to chemo- and hormone therapy, no significant difference was observed between subgroups of subjects. Amplification was also associated (p = 0.02) with the risk of multifocal distant metastases (i.e., metastases detected concomitantly in at least 2 sites) and, thus, with BC aggressiveness. These data show the importance of c-erbB-2 gene amplification in predicting the long-term outcome of patients and in selecting eligible patients for c-erbB-2-targeted therapies.
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PMID:c-erbB-2 (HER-2/neu) gene amplification is a better indicator of poor prognosis than protein over-expression in operable breast-cancer patients. 1140 Jan 21


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