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)

Spindle cell carcinoma of the breast, a variant of metaplastic carcinoma, includes a wide spectrum of lesions with histomorphologic and nuclear features ranging from overtly malignant to mildly atypical. Spindle cell carcinomas with mildly atypical features may resemble fasciitis, fibromatosis, or myofibroblastic tumors and therefore are often misinterpreted as such. A recent study has suggested that spindle cell carcinomas with a dominant fibromatosis-like phenotype, unlike spindle cell carcinomas in general, have no propensity for distant metastasis and should be termed "tumors" rather than "carcinomas." To investigate the question of fibromatosis-like spindle cell breast carcinoma (FLSpCCs) metastatic potential, we studied cases of FLSpCC seen at the University of Texas M.D. Anderson Cancer Center between 1987 and 2000. Clinical, pathologic, and immunophenotypic features were reviewed, with emphasis on biologic behavior and predictors of clinical outcome. Our series included 24 women who ranged in age from 55 to 85 years (mean 66 years). Tumor size ranged from 1.0 to 5 cm (mean 2.8 cm). Most tumors were grossly well defined but had microscopic infiltrative borders. Tumors showed a dominant fibromatosis-like or myofibroblastic-like growth pattern with prominent collagenization. Inflammatory infiltrate was noted in the majority of tumors. Cytokeratin-positive cells were seen in all cases and usually appeared as cords or sheets of polygonal cells; isolated cytokeratin-positive cells were rare. In most tumors immunoreactivity for smooth muscle actin (SMA) was confined to the cytokeratin-negative cells. In five cases intense co-expression of cytokeratin and SMA was noted. None of the tumors showed immunoreactivity for smooth muscle heavy chain myosin, estrogen receptors, progesterone receptors, or HER-2/neu. Ki-67 expression was noted in fewer than 5% of tumor cells. Treatment consisted of local excision (seven cases) or modified radical mastectomy (13 cases). Treatment was unknown in four cases. In patients who underwent axillary nodal dissection, no lymph node metastases were found. Two of the six patients who underwent local excision developed local recurrence. Two patients who underwent modified radical mastectomy developed lung metastases within 2 years after the initial diagnosis. The metastatic tumors were histologically similar to the primary tumors. Our findings indicate that FLSpCCs have the potential for local recurrence and distant metastasis and should be treated accordingly. Because FLSpCCs may be underdiagnosed as benign, the use of immunohistochemical studies, especially for cytokeratins and SMA, is essential in the evaluation of any spindle cell proliferations of the breast.
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PMID:Low-grade (fibromatosis-like) spindle cell carcinoma of the breast. 1147 84

Immunostaining for epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3, c-erbB-4, ER, and PR was performed in 107 cases of primary breast carcinomas from Anyang, China. The expression rates of EGFR, c-erbB-2, c-erbB-3 and c-erbB-4 in this series were 43.9%, 36%, 27%, and 45.8%, respectively, and a stronger c-erbB-4 staining of "normal" glandular structures inside tumors and in the vicinity of tumor clusters was confirmed. Larger tumor size, lymph node metastases, and higher histologic grade in invasive ductal carcinomas were shown to be statistically valuable negative prognostic factors, and c-erbB-2 expression was also weakly associated with a poor prognosis no matter what the nodal status. The expressions of c-erbB-4 and ER in invasive ductal carcinomas were inversely associated with histologic grade of the tumors. Associations between the expression of c-erbB-4 and ER (p = 0.001) and the expression of ER and PR study (p = 0.004) were found in the present study. No significant associations between the expressions of EGFR, c-erbB-3, c-erbB-4, ER, and PR and overall survival were detected. The expression of c-erbB-4 in the node negative group was, however, associated with a better prognosis, indicating a different role of c-erbB-4 protein in breast tumor development than other EGFR family members have. Int J Surg Pathol 9(3):177-187, 2001
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PMID:Type 1 protein tyrosine kinases in Chinese breast carcinomas: a clinicopathologic study. 1158 14

Due to the fact that capillary vessels provide not only supply of nutrients to the tumor but also represent a gate for lymphogenous and hematogenous metastatic spreading of the tumor, angiogenesis has gained increasing attention in recent years. The aim of the project was: 1. to study number of capillaries in the tumor and its relationship to the metastatic potency and prognosis and 2. to analyse the differences in the quantity of the capillaries between the groups of tumors with or without previously performed aspiration biopsy. 142 cases of breast carcinoma diagnosed at the Fingerland's Department of Pathology in the years 1997-98 were examined. Endothelial cells were visualized immunohistochemically using an antibody against factor VIII (von Willebrand factor). Capillary vessels were counted at 200x magnification (using eyepiece graticule) in the areas of highest angiogenic activity (hot spots), usually at the periphery of the tumor. The highest microvessel counts (HMC) were correlated with other factors (age, tumor size, grade, nodal status, expression of hormonal receptors, proliferative activity, p53, HER-2/neu). The differences between the tumors with and without previous aspiration biopsy were analyzed. All patients were women aged 31-86 years (median 59). The size of tumors was 4-70 mm (median 20 mm). Sixty cases have been previously examined by fine needle aspiration cytology; 72 cases were node-positive. HMC values varied from 26 to 185 (average 63.9, median 60) per microscopic field (area 0.24 mm2). The HMC was significantly higher in node-positive tumors (median 57.5 versus 66; p = 0.036). The capillary vessel counts did not correlate with other parameters examined. Fine needle aspiration cytology does seem to increase the number of intratumoral capillary vessels only for a transitory period. We have also compared HMC/mm2 in normal breast tissue with counts in carcinoma. Interestingly, the values in normal lobules, were significantly higher (median 565 versus 243; p < 0.0000001).
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PMID:[Angiogenesis in breast carcinoma. Immunohistochemical study of 142 cases]. 1166 26

We studied the profile of four c-erbB receptors in head and neck squamous cell carcinomas (HNSCC) and to determine whether their expression was associated with clinicopathological features and key molecules involved in angiogenesis and metastasis. We also assessed the impact of expression on survival. This study included 54 cases of primary HNSCC, of which 27 cases showed lymph node metastasis. The expression of c-erbB receptors, matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) family members was analysed in the same tissue homogenates by semi-quantitative RT-PCR. HNSCC frequently co-expressed multiple c-erbB receptors and showed significant correlations amongst their levels. High expression of epidermal growth factor receptor (EGFR), c-erbB-2 or c-erbB-3 was associated with an infiltrating mode of invasion, nodal metastases and advanced pathological stages. EGFR and c-erbB-2 levels were strongly correlated (P=0.0004-0.029) with the expression of MMP-2, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, VEGF-A and VEGF-C whereas the levels of c-erbB-3 and B-4 showed a weaker correlation (P=0.049-0.01) with some MMPs and VEGF-C. Only nodal metastasis and EGFR levels were significantly associated with poor outcome in uni- and multi-variate analysis. We conclude that co-operative signalling of all four c-erbB receptors may play a significant role in the pathogenesis of HNSCC. Amongst these, EGFR appears to be the dominant component controlling the invasive and angio-/lymphangiogenic phenotype in HNSCC via upregulation of multiple MMPs and VEGFs.
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PMID:C-erbB receptors in squamous cell carcinomas of the head and neck: clinical significance and correlation with matrix metalloproteinases and vascular endothelial growth factors. 1175 24

The human proto-oncogene c-erbB-2/neu gene, which is structurally similar to the epidermal growth factor receptor gene, encodes a transmembrane protein of 185 kDa (p185) with tyrosine kinase activity. Paraffin-embedded sections from 42 cases with lung carcinoma were stained immunohistochemically using the Avidin-Biotin Horseradish Peroxidase method to search for c-erbB-2 reaction. Results were evaluated semiquantitatively. The c-erbB-2 expression from each case was compared according to tumor type, grade, mitotic activity, clinical stage and lymph node metastasis. Results were statistically analyzed by using chi-square tests. We were unable to detect a significant relation between c-erbB-2 expression and histological grade, nodal metastasis, number of mitotic figures or tumor type, but we did observe a statistically significant correlation between clinical stage and increased c-erbB-2 expression (p < 0.05). In our opinion, c-erbB-2 expression in human lung carcinomas may be useful for determining clinical outcome.
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PMID:Prognostic factors and c-erbB-2 expression in non-small-cell lung carcinoma (c-erbB-2 in non-small cell lung carcinoma). 1184 6

Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin beta 1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged <50 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin beta 1-expressing stromal cells (P=0.017). Neither Akt-1 nor pAkt was related with other factors. Tumour cells-derived heregulin beta 1 was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer.
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PMID:Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. 1187 May 34

HER-2/neu peptides have recently been shown to induce a proliferative response by peripheral CD4(+) T cells in breast cancer patients. To investigate potential differences in the local cellular immune response between breast cancer patients with and without nodal metastases, lymphocytes were isolated from axillary lymph nodes from patients with breast cancer, and proliferative and cytokine responses to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20 x 10(5) cells per well in triplicate. Cells were stimulated with HER-2/neu peptides at 50 microg/ml and with control antigens. Incorporation of tritium-labeled thymidine was determined 4 days later. The levels of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10 were determined at priming and at restimulation with HER-2/neu peptides using a cytokine-specific, double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated from the axillary lymph nodes of the patients mounted significant cellular immune response to HER-2/neu peptides, manifested by proliferation and specific cytokine elaboration. Proliferative responses to HER-2/neu peptides were seen in lymphocytes of patients with and without overexpression of HER-2/neu in the primary tumor. In some patients, the proliferative response to HER-2/neu peptides in lymphocytes from lymph nodes with metastases was absent or blunted compared with the response in lymphocytes from lymph nodes without metastases from the same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type 1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast cancer patients. A Th1-specific cytokine production pattern was maintained at priming and restimulation with HER-2/neu peptides and was amplified with IL-12 costimulation. These results indicate that HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. This activation is associated with a predominantly Th1 cytokine response, which suggests that conditioning with HER-2/neu peptides may be of value in the development of breast cancer vaccines.
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PMID:Axillary lymph node cellular immune response to HER-2/neu peptides in patients with carcinoma of the breast. 1206 Apr 97

The adhesive glycophosphoprotein (OPN) is capable of inducing metastasis in rodent models ofbreast cancer. We now show that a monoclonal antibody to rat OPN recognizes specifically human OPN using Western blotting techniques andused it to assess the prognostic significance of OPN in primary tumors of a group of 333 patients treated between 1976 and 1982 for operable stage I and stage II breast cancer. The antibody stains immunocytochemically normal breast tissue weakly but pregnant/lactating tissue and 66% of the carcinomas strongly, leaving the remaining 34% as negatively stained. In addition to the carcinoma cells, some host reactive stromal cells, macrophages, lymphocytes, and blood vessels are also stained, but these have been excluded in the following analyses. There is a significant association of staining of carcinomas for OPN with some tumor variables reported previously to be associated with patient outcome: high histological grade (P = 0.024), staining for c-erbB-3 (P < 0.001), p53 (P = 0.014), pS2 (P = 0.025), and borderline significance for progesterone receptor (P = 0.089). The association of staining for OPN with survival times of the patients has been evaluated using life tables over 14-20 years of follow-up (mean 16 years) and analyzed using generalized Wilcoxon statistics. Of the patients who have been classified as OPN-negative, 94% are alive, but only 26% of those classified as OPN-positive are alive after 19 years of follow-up. This association is highly significant (P < 0.0001); the former have a median survival of >228 months and the latter 68 months. When the patients are divided into separate classes based on the percentage of carcinoma cells staining for OPN, the five classes show a progressive decrease in survival with increasing percentage of stained carcinoma cells, and this association is also highly significant (P < 0.0001). Other tumor variables that show a significant association with patient survival times in this group of patients include nodal status, tumor size, histological grade, staining for c-erbB-2, estrogen receptor alpha, or p53. Analysis of the association of patients with carcinomas staining for OPN and their survival in subgroups defined by these tumor variables shows that positive staining for OPN in each subgroup is associated with poorer survival. There is little difference in patient survival times in the OPN-negative group of patients with or without any of the other tumor variables examined. Multivariate regression analysis for 202 patients shows that staining for OPN is most highly correlated with patients' deaths (P < 0.0001), but involved lymph nodes (P = 0.0007), fixed tumors (P = 0.0008), and staining for estrogen receptor alpha (P = 0.008) are also significant independent prognostic variables with that for c-erbB-2 being of borderline significance (P = 0.060). These results suggest that in this group of patients, the presence of the metastasis-associated protein OPN is tightly correlated with patient demise.
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PMID:Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. 1206 84

Molecular prognostic and predictive factors have extensively been studied in different cancers during the past decades, some of which were found to be useful in diagnosis, follow up or even treatment of some malignant tumors. To assess the significance of c-erbB-1, c-erbB-2 and p53 expression in head and neck tumors among Iranian patients and their correlation with known prognostic factors, samples from 53 patients with squamous cell carcinomas of larynx and tongue were studied immunohistochemically. Strong immunoreactivity of c-erbB-1, c-erbB-2 and p53 was observed in 37 (70%), 40 (76%) and 37 (70%) of cases, respectively. The coexpression of these molecules was detected in 27 (50.9%) samples. Neither histological grading nor nodal involvement revealed correlation with c-erbB-1 and/or c-erbB-2 expression. No correlation was found between p53 expression and histological grade. However, a significant positive association was observed between p53 expression and nodal involvement. This data, which is the first report on head and neck squamous cell carcinomas (HNSCC) in Iran, indicates the significance of p53 protein expression which may result from p53 tumor suppressor gene inactivation in lymph node metastasis of HNSCC among Iranian patients.
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PMID:The expression of p53, c-erbB-1 and c-erbB-2 molecules and their correlation with prognostic markers in patients with head and neck tumors. 1212 95

Amplification of the c-erbB-2 oncogene and protein overexpression are well-known in breast cancer and a basis for therapy with the monoclonal antibody trastuzumab, which binds to the receptor encoded by c-erbB-2. Regarding bladder carcinoma, several studies have examined c-erbB-2 expression, but their results are quite heterogeneous. In the present study, we evaluated the expression of this oncoprotein immunohistochemically in 203 muscle-invasive urothelial bladder carcinomas using the HercepTest. Additionally, 42 cases were studied for gene amplification by fluorescence in situ hybridization (FISH) using the PathVysion kit. Follow-up was known in 147 patients. The results were compared with pathologic characteristics and disease-related survival. Immunohistochemical c-erbB-2 overexpression was observed in 37% of the tumors (76/203). However, only 5% (2/42) showed amplification of the oncogene, indicating that predominantly other mechanisms than gene amplification may cause protein overexpression in bladder cancer. C-erbB-2 protein overexpression was significantly associated with high tumor grade (p=0.004) and infiltrative growth pattern (p=0.0001), and tendentiously associated with the presence of lymph node metastases (p=0.077). Regarding tumor stage, sex and age, no significant correlation was registered. Kaplan-Meier curves showed a significantly worse disease-related survival for patients with c-erbB-2 overexpressing tumors (p=0.0346 by log-rank test). Multivariate analysis revealed that, besides nodal status (p=0.0001) and tumor stage (p=0.028), c-erbB-2 overexpression was an independent predictor of disease-related survival (p=0.030). Thus, our results suggest that immunohistochemical c-erbB-2 detection might represent an additional tool in determining bladder cancer prognosis. Clinical trials evaluating the efficacy of trastuzumab therapy in bladder cancer patients are warranted.
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PMID:Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome. 1237 Jul 44


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