Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular signatures associated with malignant phenotype would be useful for detection of micrometastatic carcinoma cells. The small breast epithelial mucin (SBEM) gene is predicted to code for a low molecular weight glycoprotein. To evaluate its potential role as a marker for bone marrow (BM) micrometastasis in breast cancer (BC) patients, we have studied in silico and in vitro expression profiles of SBEM gene. Digital SBEM expression in libraries obtained from normal and neoplastic tissues and cell-lines (CL) were displayed and counted on the SAGE Anatomic Viewer. Profiles for cytokeratin-19 and mammaglobin (hMAM), commonly targets used for detection of disseminated BC cells were obtained and compared with SBEM data. Human breast and haematopoietic cancer CL and normal BM were examined by RT-PCR for SBEM and hMAM. Bioinformatics tools were used to gain further insights about the biological role of SBEM in normal breast and BC. Genes with expression patterns in breast libraries correlating with SBEM were identified using two-dimensional display. SBEM tag was detected in 40 libraries (21 BC; 8 non-cancerous breast tissues). Intermediate to high expression was found on 15/21 BC libraries and 7/8 non-tumor breast tissue. SBEM tag count was correlated with ERBB2 (0.662), hMAM (0.409), and RRM2 (-0.379). A model system based on RT-PCR for SBEM mRNA was highly sensitive and specific in order to detect isolated tumor cells. Our results demonstrate that SBEM mRNA may be an imp ortant marker for targeting BC micrometastasis.
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PMID:In silico and in vitro analysis of small breast epithelial mucin as a marker for bone marrow micrometastasis in breast cancer. 1849 56

The stratified squamous epithelium of the nipple-areola complex may contain pale cells including: Paget's disease cells (PDCs), Toker cells (TCs), and so-called clear cells (CCs). PDCs are atypical, commonly concentrated along the basal layer. They stain for EMA, CAM5.2, cytokeratin 7, and HER2/neu oncoprotein. TCs are bland cells with roundish and scant-chromatin nuclei. TCs are reactive for EMA, CAM5.2, and cytokeratin 7, but show negativity for HER2/ neu oncoprotein. The majority of cells that have been called epidermal CCs fit the features of pagetoid dyskeratosis, reactive for high molecular weight cytokeratin. Other CCs showing signet-ring morphology correspond to a fixation artefact.
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PMID:[Clear and pale cells of the nipple epidermis: a critical study of their varieties]. 1859 14

Collecting duct carcinoma is a highly aggressive renal epithelial malignancy, although it accounts for less than 1% of the incidence of renal epithelial neoplasms. Differential diagnoses between collecting duct carcinoma, pelvic urothelial carcinoma with marked invasion to the renal parenchyma (invasive urothelial carcinoma), and papillary renal cell carcinoma is often challenging. In our current study, we examined the utility of using commercially available antibodies, in conjunction with lectin histochemistry, for such differential diagnoses. We examined 17 cases of collecting duct carcinoma, 10 cases of invasive urothelial carcinoma and 15 cases of papillary renal cell carcinoma (type 1, 6 cases; type 2, 9 cases) in these evaluations. Our results indicated that Ulex europaeus agglutinin 1, E-cadherin, and c-KIT were frequently positive in collecting duct carcinoma and invasive urothelial carcinoma, in comparison with papillary renal cell carcinoma, which had negative results for CD10 and alpha-methylacyl CoA racemase. We found, however, that collecting duct carcinoma showed positivity for high-molecular-weight cytokeratin and low-molecular-weight cytokeratin at a low frequency compared with invasive urothelial carcinoma, and that these distinctions need further careful evaluation. In addition, high-molecular-weight cytokeratin positivity was not a reliable marker for collecting duct carcinoma. We conclude that Ulex europaeus agglutinin 1 reactivity and positivity for E-cadherin and c-KIT are effective in distinguishing collecting duct carcinoma from papillary renal cell carcinoma, and that negative results for alpha-methylacyl CoA racemase and CD10 are potentially useful hallmarks of this distinction also. In contrast, a differential diagnosis for collecting duct carcinoma and invasive urothelial carcinoma will require careful examination of multiple routinely stained specimens, particularly in cases of in situ neoplastic lesions in the pelvic mucosa.
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PMID:Collecting duct carcinoma of the kidney: an immunohistochemical evaluation of the use of antibodies for differential diagnosis. 1860 72

The aim of present study is to explore the immunohistochemical profiles of brain metastases from breast cancer. We retrospectively performed immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2/neu), and cytokeratin (CK) 5/6 in 29 patients with resected tumor specimens of brain metastases. Immunohistochemical staining for ER, PgR and HER2/neu was performed in 24 patients with primary tumors. The positive frequency of immunohistochemical profiles of ER, PgR, HER2/neu, and CK5/6, in the brain metastases were 13.8%, 6.9%, 37.9%, and 24.1%, respectively. The immunohistochemical profiles including ER, PgR, and HER2/neu of the primary tumor and the brain metastasis differed in seven patients (29.2%, N = 7/24). Interestingly, the biological characteristics of brain metastasis sometimes changed which were represented by immunohistochemical staining. Therefore, the changes in the biological features of breast cancer should be taken into account when developing treatment strategies, including new molecular-targeted drugs, for brain metastases.
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PMID:Immunohistochemical profiles of brain metastases from breast cancer. 1864 8

Breast cancer in the young is considered a special clinical presentation of the disease. Sixty-nine breast cancer cases diagnosed at or before the age of 35 were analyzed for common morphological and immunophenotypical features of basal-like carcinomas. Sixteen carcinomas displayed the immunophenotypical characteristics (estrogen receptor and HER2 negativity and positivity for at least one of the following basal markers: cytokeratin 5 or 14, epidermal growth factor receptor, p63) of basal-like carcinomas, and most of them demonstrated characteristic histological features (pushing borders, lymphocytic peritumoral infiltrate, central hypocellular zone or necrosis, high mitotic rate) too. These tumors were more likely to be high-molecular-weight cytokeratin: 34betaE12 and p53 positive by immunohistochemistry. The presence of a basal-like phenotype can be important as concerns systemic treatment issues and could theoretically be associated with a higher rate of BRCA1 mutations in the young, because of the overlap of BRCA1 mutation associated breast carcinomas and the basal-like phenotype.
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PMID:Basal phenotype in breast carcinoma occurring in women aged 35 or younger. 1875 48

Spindle cell lesions of the urinary bladder are uncommon, but when encountered in clinical practice, pose a difficult diagnostic challenge as the differential diagnostic considerations are vast. Pseudosarcomatous processes significantly overlap with malignant tumors (sarcomatoid urothelial carcinoma and leiomyosarcoma) in their morphology and published immunohistochemical profile [pancytokeratin pan (CK), smooth muscle actin (SMA), and desmin]. p63 has been studied rarely and CK 5/6 and CK 34betaE12 have not been analyzed in the bladder in this diagnostic context. In the current study, 45 typical examples of spindle cell lesions [10 pseudosarcomatous myofibroblastic proliferations (PMP), 22 sarcomatoid urothelial carcinomas, and 13 smooth muscle tumors] of the urinary bladder were immunostained with a panel containing broad spectrum anticytokeratin antibodies (OSCAR or AE1/AE3), as well as antibodies to CK 34betaE12, CK 5/6, p63, SMA, and anaplastic lymphoma kinase (ALK). The immunoreactivity was as follows: PMP-CK (OSCAR) 7/10 (70%), CK (AE1/AE3) 7/9 (78%), CK 34betaE12 0/10 (0%), CK 5/6 0/9 (0%), p63 0/9 (0%), SMA 10/10 (100%), ALK 2/10 (20%); sarcomatoid urothelial carcinoma-CK (OSCAR) 15/22 (68%), CK (AE1/AE3) 14/20 (70%), CK 34betaE12 5/20 (25%), CK5/6 6/22 (27%), p63 11/22 (50%), SMA 16/22 (73%), ALK 0/22 (0%); and smooth muscle tumors-CK (OSCAR) 7/13 (54%), CK (AE1/AE3) 7/12 (58%), CK 34betaE12 0/12 (0%), CK 5/6 0/12 (0%), p63 3/13 (23%), SMA 11/13 (85%), ALK 0/13 (0%). Positivity for keratin was typically focal to moderate in smooth muscle tumors and more commonly moderate to diffuse in sarcomatoid carcinomas and PMP. Our data indicate that there is significant immunohistochemical overlap between the different spindle cell lesions, each of which has unique clinicopathologic, prognostic, and therapeutic ramifications. Within the context of morphology, an immunohistochemical panel composed of broad-spectrum antibodies to cytokeratin as well as antibodies to SMA, ALK, p63, and CK 5/6 will be a useful diagnostic adjunct: a combination of pankeratin, SMA, and ALK positivity favors PMP; expression of several cytokeratin and especially CK 34betaE12 and CK 5/6 with p63 favors sarcomatoid carcinoma and SMA positivity with overall absence of other markers favors leiomyosarcoma.
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PMID:Utility of a comprehensive immunohistochemical panel in the differential diagnosis of spindle cell lesions of the urinary bladder. 1894 4

Pregnancy results in the transfer of stem cells from the fetus to the maternal circulation. These cells are able to migrate and differentiate within various damaged maternal tissues. We recently showed the presence of fetal-derived cells in human breast carcinomas during pregnancy. In this study, we aimed to reproduce these results in a murine model of "pregnancy-associated" breast carcinoma. We bred virgin MMTV-H-Ras transgenic female mice with male mice transgenic for luciferase under the control of the VEGFR2 promoter. Tumors that developed during or following gestation were analyzed and their nuclear grade classified. Fetal cells were detected by Y chromosome Fluorescence in situ hybridization FISH in 9/9 of breast carcinomas but only in 2 liver controls from the same animals. The number of fetal cells was 20 and 4.9 per million maternal cells in these tissues, respectively (p < 0.05). High grade tumors had significantly more fetal cells (p < 0.05). In vivo imaging of the luciferase signal under control of the VEGFR2 promoter as well as von Willebrand staining did not reveal an endothelial phenotype of fetal cells. Sixty two percent of the fetal cells expressed cytokeratins but were not tumoral. In conclusion, fetal cells-expressing cytokeratin-are always present in murine breast carcinomas associated with gestation. Interestingly, high-grade tumors contain more fetal cells.
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PMID:Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy. 1906 66

The author reports herein two cases of ductal adenoma of the breast with an emphasis on immunohistochemistry. Both cases (patient 1, 58-year-old woman; patient 2, 78-year-old woman) were clinically suspected as carcinoma, and core biopsies were 'indeterminate' or 'suspicious for malignancy'. Excisional biopsy and wide excision were performed. Histologically, both cases were ductal adenomas composed of ductal epithelial cells and myoepithelial cells. Patient 1 had extensive apocrine metaplasia. Immunohistochemically, myoepithelial cells were noted in both cases; cytokeratin (CK) 14 and p63 were the most reliable myoepithelial markers, followed by CD10, alpha-smooth muscle actin and S100 protein. CK profile was as follows: positive expression of CK5/6, CK18, CK19, and high-molecular-weight CK, and negative expression of CK20. This CK profile was the same as that of non-tumorous ducts, suggesting that the CK profile does not alter in tumorigenesis. The tumor cells expressed p53 protein (case 1, positive cell percentage 5%; case 2, 7%), c-erbB2 (HER2/neu, 76%, 64%), CEA (5%, 0%), estrogen receptor (33%, 84%), but were negative for progesterone receptor. Ki-67 labeling was 5% and 3%, respectively. MUC apomucin expression was as follows: MUC1, 92%, 100%; MUC2, 0%, 0%; MUC5AC, 0%, 0%; and MUC6, 5%, 0%. Non-tumorous ducts expressed MUC1, but were negative for MUC2, MUC5AC and MUC6.
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PMID:Ductal adenoma of the breast: immunohistochemistry of two cases. 1906 57

The stratified squamous epithelium of the nipple-areola complex may contain pale or clear cells including: Paget's disease cells (PDCs), Toker cells (TCs), and so-called clear cells (CCs). Paget's disease is an uncommon presentation of breast carcinoma. PDCs are large, atypical, have abundant, pale-staining cytoplasm that may contain mucin secretion vacuoles and bulky heterochromatic nuclei. They are commonly concentrated along the basal layer and stain for EMA, CAM5.2, cytokeratin 7, and HER2/neu oncoprotein. TCs are bland cells with roundish and scant chromatin nuclei. They are found incidentally and are reactive for EMA, CAM5.2, and cytokeratin 7, but show negativity for HER2/neu oncoprotein. So-called CCs show varied morphology, are found incidentally, and have been variably interpreted by different authors. The majority of cells that have been called epidermal CCs fit the features of pagetoid dyskeratosis. These cells are reactive for high molecular weight cytokeratin. Other CCs showing signet-ring morphology present negativity for mucins and correspond to a fixation artefact.
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PMID:An overview of the pale and clear cells of the nipple epidermis. 1913 Apr 6

Human endometrium is a highly regenerative tissue undergoing more than 400 cycles of growth, differentiation, and shedding during a woman's reproductive years. Endometrial regeneration is likely mediated by adult stem/progenitor cells. This study investigated key stem cell properties of individual clonogenic epithelial and stromal cells obtained from human endometrium. Single-cell suspensions of endometrial epithelial or stromal cells were obtained from hysterectomy tissues from 15 women experiencing normal menstrual cycles, and were cultured at clonal density (10 cells/cm(2)) or limiting dilution. The adult stem cell properties-self-renewal, high proliferative potential, and differentiation of single epithelial and stromal cells-were assessed by harvesting individual colonies and undertaking serial clonal culture, serial passaging, and culture in differentiation-induction media, respectively. Lineage differentiation markers were examined by RT-PCR, immunocytochemistry, and flow cytometry. Rare single human endometrial EpCAM(+) epithelial cells and EpCAM(-) stromal cells demonstrated self-renewal by serially cloning >3 times and underwent >30 population doublings over 4 mo in culture. Clonally derived epithelial cells differentiated into cytokeratin(+) gland-like structures in three dimensional culture. Single stromal cells were multipotent, as their progeny differentiated into smooth muscle cells, adipocytes, chondrocytes, and osteoblasts. Stromal clones expressed mesenchymal stem cell (MSC) markers ITGB1 (CD29), CD44, NT5E (CD73), THY1 (CD90), ENG (CD105), PDGFRB (CD140B), MCAM (CD146) but not endothelial or hemopoietic markers PECAM1 (CD31), CD34, PTPRC (CD45). Adult human endometrium contains rare epithelial progenitors and MSCs, likely responsible for its immense regenerative capacity, which may also have critical roles in the development of endometriosis and endometrial cancer. Human endometrium may provide a readily available source of MSCs for cell-based therapies.
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PMID:Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. 1922 91


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