Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MUC1 mucin is a heavily O-glycosylated transmembrane protein that is aberrantly expressed in many carcinomas, including breast cancer. In the present study, the effect of signaling generated from the Erb-B2 homodimer as a result of transcription of the MUC1 gene was investigated in human mammary epithelial cell lines (MTSV1-7 and Hb2) stably transfected with a pBAT/trk-neu construct in which the extracellular domain of Erb-B2 was replaced with the corresponding domain from the nerve growth factor (NGF) receptor. In this system, NGF stimulated homodimerization of Erb-B2 and phosphorylation of its intracellular domain. MTSV1-7/trk-neu and Hb2/trk-neu cells were transiently transfected with a construct in which the MUC1 promoter caused expression of a CAT reporter gene, and were then treated with NGF. These studies showed that MUC1 expression was inhibited by NGF treatment in both cell lines, suggesting that its expression can be regulated by signals resulting from the homodimerization of Erb-B2.
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PMID:Erb-B2 homodimerization inhibits MUC1 transcription in cultured human mammary epithelial cells. 1279 75

Salivary duct carcinoma is a relatively uncommon aggressive neoplasm, typically found in the parotid glands of older men. The histologic appearance is that of an in situ and invasive high-grade adenocarcinoma, and it closely resembles ductal carcinoma of the breast. Several variants of the latter are very well known, but only papillary, sarcomatoid, and low-grade subtypes have so far been reported in salivary duct carcinoma. This study describes the clinicopathologic and immunohistochemical findings in four examples of an additional previously undescribed variant, rich in mucin. Each tumor showed areas of typical salivary duct carcinoma, but in addition there were lakes of epithelial mucin-containing malignant cells, i.e., mucinous (colloid) carcinoma. All four tumors expressed androgen receptors, cytokeratins, epithelial membrane antigen, gross cystic disease fluid protein-15, and carcinoembryonic antigen, but S-100 protein, other myoepithelial markers, and estrogen and progesterone receptors were negative. The mucin antigen profile showed positivity for MUC2, MUC5B, and MUC6 in all cases but only rare staining with MUC5AC and MUC7. Strong immunohistochemical overexpression of HER2/neu was demonstrated in one tumor, together with amplification by fluorescence in situ hybridization; another case was weakly positive with just one antiserum, but the remaining two tumors were completely negative. Small quantities of mucin have often been described in salivary duct carcinoma but not large extracellular mucinous lakes, which though prominent in the present series, were not as extensive as in mucinous adenocarcinoma. The relatively poor clinical outcome of the patients in our study mirrored that seen in usual-type salivary duct carcinoma and emphasizes the importance of differentiating mucin-rich salivary duct carcinoma from pure mucinous (colloid) adenocarcinoma, a tumor not fully defined, but possibly with a better prognosis.
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PMID:Mucin-rich variant of salivary duct carcinoma: a clinicopathologic and immunohistochemical study of four cases. 1617 3

The MUC4 mucin is a high molecular weight membrane-bound glycoprotein. It is aberrantly expressed in pancreatic tumors and tumor cell lines with no detectable expression in the normal pancreas. A progressive increase of MUC4 expression has also been observed in pancreatic intraepithelial neoplasia, suggesting its association with disease development. Here, we investigated the consequences of silencing MUC4 expression in an aggressive and highly metastatic pancreatic tumor cell line CD18/HPAF that expresses high levels of MUC4. The expression of MUC4 was down-regulated by the stable integration of a plasmid-construct expressing antisense-MUC4 RNA. A decrease in MUC4 expression, confirmed by Western blot and immunofluorescence analyses, resulted in diminished growth and clonogenic ability of antisense-MUC4-transfected (EIAS19) cells compared with parental, empty vector (ZEO) and sense transfected (ES6) control cells. In addition, EIAS19 cells displayed a significant decrease in tumor growth and metastatic properties when transplanted orthotopically into the immunodeficient mice. In vitro biological assays for motility, adhesion, and aggregation demonstrated a 3-fold decrease in motility of EIAS19 cells compared with control cells, whereas these cells adhered more and showed an increase in cellular aggregation. Interestingly, MUC4 down-regulation also correlated with the reduced expression of its putative interacting partner, HER2/neu, in antisense-MUC4-transfected cells. In conclusion, the present work demonstrates, for the first time, a direct association of the MUC4 mucin with the metastatic pancreatic cancer phenotype and provides experimental evidence for a functional role of MUC4 in altered growth and behavioral properties of the tumor cell.
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PMID:Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis. 1474 77

Although fine-needle aspiration cytology is a routine procedure for the diagnosis of breast carcinoma, cytologic specimens have rarely been used for evaluation of hormone receptor status and HER2/neu overexpression. In order to compare the biological markers on cytology and on histology, routinely fixed smears of 110 primary breast carcinomas were immunostained for estrogen receptor (ER), progesterone receptor (PgR), and HER2/neu by automated immunostainer and the results were compared with the corresponding histologic sections. ER was expressed in 76 of 110 (69%) cases and PgR was expressed in 51 of 110 (46%). Overexpression of HER2/neu was observed in 30 of 110 (27%) cases. Concordance between cytology and histology was 98% for ER, 95% for PgR, and 100% for HER2/neu. There was no false positive result on smears. Diagnostic pitfalls in determination of hormone receptor status on smears included intratumoral heterogeneity and presence of mucin.
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PMID:Hormone receptor status and HER2/neu overexpression determined by automated immunostainer on routinely fixed cytologic specimens from breast carcinoma: correlation with histologic sections determinations and diagnostic pitfalls. 1504 60

An 83-year-old woman with long-standing chronic ischemic cardiac and obstructive pulmonary disease, presented with a painless tumor in her right breast. Microscopically the tumor consisted of micropapillary formations and loosely cohesive nests and strands of large, highly pleomorphic cells. Micropapillary formations were surrounded by peritumoral retraction clefting, and the papillae lacked a true fibrovascular core. Multinucleated giant and bizarre tumor cells were also present and numerous. Within the tumor a high-grade intraductal component with the same cell morphology and necrosis and mucin production was found. Micropapillary pattern occupied approximately 60% of the tumor mass, loosely cohesive nests and strands approximately 20% and an intraductal component was noted in approximately 20% of the tumor mass. On immunohistochemistry the tumor cells were positive for pan-cytokeratin, epithelial membrane antigen (EMA), S100 protein and E-cadherin while estrogen and progesterone receptors, HER2-neu and Bcl2 were negative. EMA staining was diffuse and observed in the outer and inner margins of neoplastic nests. The diagnosis of pleomorphic breast carcinoma with predominant micropapillary features was established. In summary, micropapillary carcinoma can be distinguished from other types of breast carcinoma with micropapillary growth pattern on the basis of reverse cell polarity, which is easily confirmed on immunohistochemistry.
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PMID:Pleomorphic ductal carcinoma of the breast with predominant micropapillary features. 1780 59

Mucoepidermoid carcinoma (MEC) comprises approximately 30% of all salivary gland malignancies, making it the most common malignant tumor of the salivary glands. Multiple histologic variants with a wide range of differentiation have been described. Sclerosing MEC (SMEC) is a rare subtype that may be misdiagnosed as a benign reactive condition or low-grade non-SMEC malignancy. We report 4 cases of SMEC and evaluated them with Her-2/neu and MIB-1 to determine whether an association exists between the histologic grade and immunohistochemical findings. In 3 cases, histologic examination demonstrated relatively well-circumscribed, nonencapsulated tumors composed of extensive central sclerosis with keloid-like stroma and scattered epithelial islands of low-grade MEC. In the fourth case, the tumor showed similar sclerotic stroma; but the epithelial component was of intermediate grade. In all 4 cases, eosinophils and neutrophils were part of the inflammatory infiltrate; and the edges were surrounded by lymphoid tissue, with germinal center formation and residual epithelial islands. A Mayer mucicarmine stain revealed abundant intracytoplasmic mucin. We found MIB-1 labeling indices of 5% or less in cases 1, 2, and 3 and 12% in case 4, suggesting an association between MIB-1 index and tumor grade. The tumors were negative for Her-2/neu in all 4 cases. The latter seems to bear no relationship to tumor grade.
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PMID:Sclerosing mucoepidermoid carcinoma of the salivary glands. 1802 24

Extramammary Paget's disease (EMPD) is considered to be an intraepithelial adenocarcinoma. Typically involved anatomical sites are the vulvar, perianal, perineal, scrotal and penile regions. Clinically, the lesions present as well-defined, moist, erythematous plaques usually accompanied by pruritus. An unusual feature of EMPD is its association with cutaneous, adnexal-structure adenocarcinomas and its association with internal malignancies. Histopathological examination shows epidermal acanthosis and elongated rete ridges. Paget's cells are large intraepidermal cells with a large nucleous and abundant pale cytoplasm. Recent studies of perianal and vulvar EMPD have described distinct immunohistochemical subtypes termed cutaneous and endodermal. Cutaneous EMPD is characteristically positive for cytokeratin (CK)7, negative for CK20, and positive for gross cystic disease fluid protein (GCDFP)15+, whereas endodermal EMPD shows a CK7+ CK20+ GCDFP15- phenotype. Surgery remains the treatment of choice, with either wide surgical excision or Mohs' micrographic surgery. We present a case of EMPD with an underlying carcinoma, which combined immunohistochemical findings suggestive of the cutaneous subtype (positive for CK7, GCDFP15, mucin (MUC)1, human epidermal growth factor receptor (HER)2/neu positive) and the endodermal subtype, frequently associated with internal malignancy (CK20, MUC2, CDX-2 positve); however, our patient had no associated internal malignancy.
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PMID:Extramammary Paget's disease of the groin with underlying carcinoma and fatal outcome. 1848 20

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

Invasive lobular carcinomas (ILC) of breast typically demonstrate intracytoplasmic mucin. We present a unique case of classical type ILC with abundant extracellular mucin and strong ERBB2 (HER2/neu) expression confirmed by immunohistochemistry and fluorescent in situ hybridization. Dual E-cadherin/p120 immunohistochemical stain demonstrated complete loss of membranous E-cadherin and the presence of diffuse cytoplasmic p120 staining, confirming the lobular phenotype. The tumor cells showed ductal-like cytoplasmic MUC1 staining, but were negative for MUC2 and other mucin gene markers. In addition, studies of tissue microarrays of 80 breast carcinomas with mucinous differentiation revealed 4 pure mucinous carcinomas showing significantly reduced E-cadherin staining without redistribution of p120 into cytoplasm. The findings suggest that the presence of extracellular mucin does not exclude a diagnosis of lobular carcinoma, and the morphologic and molecular characteristics of lobular and ductal carcinomas are more complex than previously appreciated.
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PMID:Invasive lobular carcinoma with extracellular mucin production and HER-2 overexpression: a case report and further case studies. 2055 Jun 96

Psammoma bodies (PBs) in breast lesions are rare and little is known about the role of these structures in breast pathology. This study has looked in to the diagnostic significance of PBs in fine needle aspiration (FNAC) of breast lesions. Over a 5-year period, FNACs of the breast were done in 4,563 subjects, of which 1,678 were diagnosed to be malignant. On review of all breast aspirates including non-neoplastic lesions, 30 cases showed PBs to be associated with breast carcinoma (BC). Cytological features were correlated with clinical, radiological, histological, and immunohistochemical findings. All 30 aspirates and their corresponding histological sections showed varying number of PBs and nonpsammomatous bodies (NPBs). For comparison, 31 cases of age-matched BC without PBs and NPBs in both aspirates and sections were studied. Statistical analysis using Chi-square test was done to compare BC with and without PBs. BC with PBs was characterized by papillary pattern of malignant cells, mucin in the background, infiltration by macrophages, cellular degeneration, overexpression of estrogen receptor (ER), and progesterone receptor (PR) and moderate positivity (2+) for Her2/neu. Calcium deposition has long been implicated in the pathogenesis of many degenerative diseases; hence the formation of PBs may be relevant in breast oncology. The presence of PBs in FNAC of clinically suspected breast lesions which are cytologically negative for malignancy warrants further histological confirmation.
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PMID:Psammoma bodies in fine needle aspiration cytology of the breast: a clinicopathological study of 30 cases. 2214 26


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