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)

Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions. In contrast, four of the five clear cell adenocarcinomas contained prominent areas with clear cells. Nephrogenic adenomas generally showed only mild cytologic atypia, whereas four of the five clear cell adenocarcinomas showed severe atypia. A single mitotic figure was identified in only two of the nephrogenic adenomas, whereas the mitotic rate in the clear cell adenocarcinomas ranged from 2 to 14 per 10 high-power fields. None of the nephrogenic adenomas showed evidence of necrosis, but focal necrosis was noted in four of the five clear cell adenocarcinomas. In general, the nephrogenic adenomas and clear cell adenocarcinomas showed negative to weak staining with CK903 but strong staining with AE1, AE3, and Cam 5.2. Variable staining was observed with Brst-3 and antibodies to S-100, CEA (monoclonal and polyclonal), LeuM-1, and CA19.9. Nephrogenic adenomas and clear cell adenocarcinomas were all negative for prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and estrogen and progesterone receptors (except for two nephrogenic adenomas, which showed only focal weak staining for estrogen receptor). Neither bcl-2 nor c-erbB-2 staining was able to discriminate between the tumors. However, strong staining for p53 was noted in each clear cell adenocarcinoma and in none of the nephrogenic adenomas. MIB-1 positivity in nephrogenic adenomas ranged from 0 to 13 (average of 5.5) per 200 cells, whereas the positive range for clear cell adenocarcinomas was 33 to 70 (average of 47) per 200 cells. In summary, histopathologic features that favor clear cell adenocarcinoma over nephrogenic adenoma include a predominance of clear cells, severe cytological atypia, high mitotic rate, necrosis, high MIB-1 positivity, and strong staining for p53.
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PMID:Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison. 986 32

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 healthy subjects, 58 patients with benign breast diseases, and 413 patients with breast cancer (186 locoregional, 185 with advanced disease, and 42 with no evidence of disease). Using 15 U/ml as the cut-off, no healthy subjects or patients with benign diseases and only 2.4% of no evidence of disease patients had elevated serum levels. Abnormal c-erbB-2 levels were found in 29% (101/370) of the patients with breast carcinoma (locoregional 9%, metastases 45.4%). CEA (cut-off 5 U/ml) and CA 15.3 (cut-off 35 U/ml) sensitivity was 18% and 16% in patients with locoregional disease and 61% and 70% in those patients with advanced disease, respectively. A trend toward higher serum levels of all three tumor markers in patients with nodal involvement or greater tumor size was found, but was statistically significant only with CEA (p < 0.01). By contrast, c-erbB-2 was related to steroid receptors, in both locoregional and metastatic tumors. When the prognostic value of these markers was evaluated, patients with abnormally high presurgical CEA and c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative (p < 0.05 and p < 0.001, respectively) and node-positive patients (p < 0.556 and p < 0.001, respectively). By contrast, no relationship was found between CA 15.3 values and prognosis. Multivariate analysis showed that CEA and c-erbB-2 were also prognostic factors. The correlation between serum and tissue levels of c-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). Serum concentrations in patients with advanced disease were related to the site of recurrence, with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum levels seem to be a useful tumor marker in the prognosis of patients with breast cancer. Using all three tumor markers, sensitivity was 35% in patients with locoregional breast cancer and 88% in patients with recurrence.
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PMID:c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value. 987 73

Atypical adenomatous hyperplasia (AAH) of the human lung is considered a possible precursor of pulmonary adenocarcinoma. However, its true biological significance remains to be clarified. The authors studied the ultrastructure of AAH in surgically resected lungs and compared it with that of coexisting adenocarcinoma in an effort to define the characteristic features of AAH. Ultrastructurally, AAH possessed oval to irregular nuclei with high nucleo-cytoplasmic ratio and large nucleoli. Development of cytoplasmic organelles was generally poorer in AAH than in adenocarcinoma. However, these differences became less apparent as the degree of atypia of AAH advanced. Both lamellar bodies and electron-dense granules were found in AAH as well as in adenocarcinoma. These results suggest a close relation of AAH with adenocarcinoma of type 2 pneumocyte or Clara cell type. Further, the results of immunohistochemical studies for surfactant apoprotein A, urine protein 1, cytochrome P-450s, CEA, p53, c-erbB-2, Ki67, and bcl-2 well reflected the ultrastructural findings. These results suggest, in accordance with previous studies, that AAH is a lesion closely related to adenocarcinoma. Further, AAH shares some characteristics of type 2 pneumocytes and Clara cells, implying that it might be derived from their common precursor.
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PMID:Comparative ultrastructural study of atypical adenomatous hyperplasia and adenocarcinoma of the human lung. 989 25

Adenocarcinomas of the breast behave clinically and epidemiologically in ways that show host resistance factors are important for outcome in addition to grade and stage of malignancy. Immune reactivity to autologous tumors is indicated by the general presence of lymphoid infiltration (LI) and regional lymph node changes; however, these changes predict favorable outcome only in non-metastatic disease. LI is characterized by CD4+ and CD8+ tumor infiltrating lymphocytes reflecting latent cell-mediated immunity (CMI). CMI and humoral immune reactivity have been demonstrated to autologous tumor and a variety of tumor-associated antigens (TAA) have been implicated including CEA, HER-2/neu, MAGE-1, p53, T/Tn and MUC-1. Immune incompetence involving CMI is progressive with the stage of breast cancer and is prognostically significant. Immunotherapy of several types has been designed to address this immunodeficiency and the TAAs involved. Animal models have employed drug therapy, cytokine transfection, vaccines with autologous tumor, cytokines like interferon alpha (IFN-alpha) and interleukin-2 (IL-2), TAA tumor vaccines, and immunotoxins with evidence of tumor regression by immunologic means. Immunotherapy of human breast cancer is a rapidly growing experimental area. Positive results have been obtained with natural IFN and interleukins, particularly in combination strategies (but not with high dose recombinant IFN or IL-2), with autologous tumor vaccine (but not yet with transfected autologous tumor); with a mucin carbohydrate vaccine (Theratope) in a combination strategy (but not with mucin core antigen) and with several immunotoxins. Combination strategies involving immunorestoration, contrasuppression, adjuvant, and immunotoxins are suggested for the future.
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PMID:The immunology and immunotherapy of breast cancer: an update. 1023 Aug 72

c-erbB-2 protein levels in tissue extracts and sera were determined in a retrospective analysis of 158 patients who underwent surgical resection of breast carcinoma by means of a sandwich enzyme immunometric assay (EIA) using monoclonal antibodies (MAbs) directed to the extracellular domain of the c-erbB-2 oncogene protein (ErbB-2). In the analysis of tissue extracts, 48 samples (30.3%) showed ErbB-2 levels exceeding 18.0 ng/mg protein (group A), while in 110 samples these levels were below 18.0 ng/mg protein (group B). Immunohistochemical examination of resected tissues using anti-c-erbB-2 antibody revealed positive staining in 93.8% (45/48) in group A and 13.6% (15/110) in group B (p < 0.00001). The proportion of patients who preoperatively showed a serum ErbB-2 value above 5.4 ng/ml was 52.1% (25/48) in group A and 10.0% (11/110) in group B (p < 0.00001). Thus, the level of ErbB-2 in tissue extracts was significantly associated with immunohistochemistry and ErbB-2 levels in preoperative sera. During follow-up, 48 patients (30.3%) developed recurrent disease: 17 in group A (35.4%) and 31 in group B (28.2%). From an ROC analysis based on the postoperative serum ErbB-2 levels in patients either with or without relapse, the cutoff value of serum ErbB-2 for tumor relapse was determined to be 6.5 ng/ml. The sensitivity of serum ErbB-2 in patients with relapsed breast cancer was 58.3% (21/36) overall, 84.6% (11/13) in group A and 43.5% (10/23) in group B. In the analysis of serum samples taken before relapse, 90.9% (10/11) of the subjects in group A and 26.7% (4/15) of those in group B were shown to be positive for serum ErbB-2. Serum ErbB-2 in group A was a more sensitive marker than other tumor markers such as CEA, CA15-3, and NCC-ST-439. Thus, the determination of ErbB-2 in tissue extracts of breast carcinoma may be useful for assessing c-erbB-2 protein expression in the primary tissue and indicates that serum ErbB-2 may be a sensitive marker for monitoring tumor relapse.
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PMID:Combined measurement of the c-erbB-2 protein in breast carcinoma tissues and sera is useful as a sensitive tumor marker for monitoring tumor relapse. 1095 6

Vaccination of patients with cancer using dendritic cells (DCs) was shown to be effective for B-cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu- or MUC1-derived peptides. Ten patients were included in this pilot study. The DC vaccinations were well tolerated with no side effects. In 5 of 10 patients, peptide-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood using both intracellular IFN-gamma staining and (51)Cr-release assays. The major CTL response in vivo was induced with the HER-2/neu-derived E75 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, suggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Our results show that vaccination of DCs pulsed with a single tumor antigen may induce immunologic responses in patients with breast and ovarian cancer. This study may be relevant to the design of future clinical trials of other peptide-based vaccines.
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PMID:Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. 1104 90

A 64-year postmenopausal woman had noticed a left breast lump 5 months before presentation and was admitted due to increasing tumor size. Physical examination showed a well demarcated, movable mass 5 cm in diameter in the upper outer quadrant of the left breast. The lesion was not painful. She had no past history of malignancy or chest wall irradiation. She had no family history of malignancy. Mammography revealed an irregular tumorous lesion with coarse calcifications in the left breast. Intracystic papillary cancer was suspected by ultrasonography. Aspiration breast cytology yielded insufficient material for diagnosis. Laboratory findings were all within the normal limits including alkaline phosphatase and three tumor markers (CEA, CA 15-3, ST-439). An excisional biopsy of the left breast tumor was performed. Histopathological examination revealed malignant phyllodes tumor with osteosarcomatous features and negative tumor margins. Positive vimentin and negative cytokeratin staining was confirmed by immunohistochemistry, suggesting that the tumor did not originate from epithelial cells of the breast. The estrogen receptor (ER) status of the tumor was negative but progesterone receptor (PgR) was weakly positive. Positive p53 nuclear immunoreaction but negative c-erbB-2 overexpression by immunohistochemical staining was observed in this tumor. There was no evidence of generalized disease. She has been well 6 months after surgery without adjuvant therapy.
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PMID:A case of malignant phyllodes tumor of the breast with osteosarcomatous features. 1118 Jul 71

We describe a very rare association between intraepithelial, extramammary Paget's disease and human papillomavirus- (HPV) negative, keratinized type of VIN III observed in two elderly women. In both cases, morphological and immunohistochemical investigation showed two heterogeneous but intimately admixed neoplastic populations of vulvar epithelium. Atypical keratinocytes stained markedly and diffusely positive for high molecular weight cytokeratins, and moderately for p53 protein and c-erbB-2 immunostainings. Paget cells were diffusely positive for CEA, EMA, and low molecular weight cytokeratins, moderately and focally for c-erbB-2 and (in one case) for S-100. Morphological and immunohistochemical phenotypic differences between Paget cells and atypical keratinocytes suggest a simultaneous and incidental association of two distinct neoplastic disorders more than a mixed carcinoma in situ of vulvar epithelium.
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PMID:Simultaneous vulvar intraepithelial neoplasia and Paget's disease: report of two cases. 1143 29

Dendritic cells (DC) are the most potent APC with the unique capacity to initiate primary immune responses. For clinical use DC can be generated in vitro from CD34+ peripheral blood progenitor cells or monocytes. Vaccination of patients with cancer using DC was shown to be effective for B-cell lymphoma, renal cell carcinoma (RCC), prostate cancer and malignant melanoma. We provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DC pulsed with HER-2/neu- or MUC1-derived peptides. In 5 of 10 patients, peptide-specific cytotoxic T lymphocytes (CTL) could be detected in the peripheral blood using both intracellular IFN-gamma staining and Cr-release assays. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after seven immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Currently we are analyzing the effect of T-helper epitopes and IL-2 on the CTL induction using peptide pulsed DC. In this ongoing trial one patient with metastatic RCC developed a partial remission of the metastatic sites was induced after the first four vaccinations with MUC1 peptides pulsed DC, that was ongoing after the next cycles containing IL-2. Vaccine-induced peptide-specific T-cell responses in vivo were detected in the PBMNC of this patient and in peptide-specific DTH reactions. This studies demonstrate that peptide pulsed DC can be effective in cancer patients and induce significant clinical and immunological responses.
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PMID:Dendritic cells in vaccination therapies of malignant diseases. 1235 54

The clinical role of HER-2/neu, a 185 kD epithelial transmembranous protein, has evolved after the approval of the anti-HER-2/neu targeted monoclonal antibody trastuzumab (Herceptin) for the therapy of metastatic breast cancer. The extracellular domain of HER-2/neu undergoes proteolytic cleavage from the full-length protein by metalloproteases, and is shed into the blood as a circulating antigen. While HER-2/neu gene amplification and/or protein overexpression are detected in approximately 25% of primary breast cancers, serum HER-2/neu levels are elevated beyond the upper limit of normal in 50 to 60% of stage IV breast cancer patients. HER-2/neu in serum can be detected by enzyme immunoassays (manual and automated versions). It has been shown to have prognostic and predictive information in breast cancer patients. Monitoring for recurrence by serum HER-2/neu reaches a high sensitivity for HER-2/neu positive tumors. Longitudinal follow-up of patients during any kind of systemic therapy allows for monitoring of the therapeutic success. When utilized in these applications, serum HER-2/neu testing is complementary to HER-2/neu tissue results and to the determination of classical tumor markers such as CA 15-3, CA 27.29 and CEA, which are not targeted by specific forms of systemic therapy.
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PMID:Serum HER-2/neu in the management of breast cancer patients. 1281 Jan 50


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