Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urothelial carcinoma with gland-like lumina is an uncommon type of tumor, reported only occasionally in literature. Its diagnosis usually does not offer any difficulties, and its prognosis is determined by the accompanying classic transitional or squamous component. It is important though, not to misdiagnose it as a mixed transitional cell adenocarcinoma. In that respect, features such as the type of epithelium lining, the gland-like structures, as well as the type of luminal mucin have been used to make the diagnosis. Recently, an immunohistochemical panel of antibodies has proven helpful in differentiating primary and metastatic adenocarcinomas of urothelial tract from urothelial carcinoma with gland differentiation. In their series of 16 cases, Tamboli et al included only one case of transitional cell carcinoma with gland differentiation. We present two additional cases of urothelial carcinoma with gland-like lumina in two men, 60 and 79 years old, respectively. Both tumors were grade 2 of Ash-Bergkvist, and the stage was pT(1) in both cases. Immunohistochemical study with cytokeratins 7 and 20, and with c-erbB-2, was performed. Both tumors expressed cytokeratins 7 and 20; c-erbB-2 was only expressed in one, in spite of the same staging. Although some relation has been found in animals between gland-like lumina phenotype and expression of epidermal growth factor (the receptor of which is homologous to c-erbB-2), it seems that this relationship might not be constant in humans.
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PMID:Expression of c-erbB-2 and cytokeratins 7 and 20 in urothelial carcinoma with gland-like lumina. 1457 29

Most pancreatic neoplasia are of ductal lineage, characterized by tubule (gland), cyst, papilla, or mucin formation and expression of mucin-related glycoproteins and oncoproteins (eg, MUC1, CA19-9, CEA, DUPAN), as well as some subsets of cytokeratin (eg, CK19). Mutations of k-ras oncogene and DPC4 are also common in ductal neoplasia and generally not seen in nonductal tumors. A variety of pancreatic neoplasia fall under the heading of ductal neoplasia. Invasive ductal adenocarcinoma (DA) is the most important and constitutes the vast majority (>85%) of pancreatic tumors. DA is characterized by insidious infiltration and rapid dissemination, despite its relatively well-differentiated histologic appearance. In some variants of DA such as undifferentiated or sarcomatoid, evidence of ductal differentiation may be lacking or only focal. The presumed precursors of DA are microscopic intraductal proliferative changes that are now termed pancreatic intraepithelial neoplasia (PanIN). PanINs comprise a neoplastic transformation ranging from early mucinous change (PanIN-1A) to frank CIS (PanIN-3). A similar (in situ) neoplastic spectrum also characterizes intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, which are cystic ductal-mucinous tumors with varying degrees of papilla formation, and may be associated with invasive carcinoma. As such, these can be regarded as mass-forming preinvasive neoplasia. Some intraductal papillary mucinous neoplasms are associated with invasive carcinoma of the colloid type. Colloid carcinoma of the pancreas appears to be a clinicopathologically distinct tumor with indolent behavior. Whereas most ductal pancreatic neoplasia are characterized by some degree of mucin formation, serous tumors, of which serous (microcystic) adenoma is the sole example, lack mucin formation, presumably because they recapitulate centroacinar ducts. They are typically benign tumors. It is recognized now that pancreatic carcinoma, like other malignant processes, is a genetic disease produced by progressive mutations in cancer-related genes. These alterations can be categorized as "early" such as k-ras mutation, HER-2/neu, PSCA, MUC5, and fascin overexpression; "intermediate" such as p16 inactivation, MUC1, and cyclin D1 overexpression; and finally as "late" such as p53 and DPC4 inactivation, BRCA2 mutation, and overexpression of ki-67, 14-3-3sigma, and mesothelin. Ductal neoplasia is the most important category among pancreatic tumors. It is important to appreciate the different types of ductal tumors because they vary greatly in their clinicopathologic characteristics and prognosis. Understanding the molecular mechanisms of ductal carcinogenesis will help develop more efficient prevention and therapy of these tumors.
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PMID:Ductal neoplasia of the pancreas: nosologic, clinicopathologic, and biologic aspects. 1618 79

Circulating proteinic biomarkers are secreted by tumor cells or by their environmental cells and they have a variable specificity. In case of breast cancer, carcino-embryonic antigen (CEA) was for a long time the only circulating biomarker used. Nowadays, the most useful biomarkers measure circulating levels of fragments of MUC1-polymorphic epithelial mucin (MUC1-PEM): cancer antigen (CA) 15.3, mucin-like carcinoma-associated antigen (MCA), CA 27-29, CA 549... They are useful for general disease follow-up. Other circulating markers belonging to keratins (tissue polypeptide antigen, TPA, TPS or Cyfra 21.1) are correlated with proliferative activity of breast tumors. More recently, the measure of the c-erb B2 circulating part (extra cellular domain, ECD) was proposed as a prognostic biomarker for breast tumors with c-erb B2 overexpression. Moreover, the determination of urinary level of trefoil factor1 (PS2-TFF1) might be useful for the follow-up of hormonodependent breast cancers. The present review describes the clinical interest of these different circulating biomarkers in case of breast cancer, emphasizing their biological characteristics.
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PMID:[Circulating proteinic biomarkers and breast cancer]. 1687 56

Mucous cell metaplasia (MCM), defined by the appearance of mucous cells in airways where mucous cells were not present, is a consistent pathologic characteristic in the peripheral airways of bronchial asthma. Under mild inflammatory conditions MCM occurs as a result of pre-existing airway epithelial cells (AECs) starting to express mucin genes and differentiating into mucous cells. Under extensive inflammatory responses, AECs proliferate, and the development of MCM involves the differentiation of pre-existing and proliferating cells into mucous cells. Epithelial cell numbers per mm basal lamina are increased by approximately 30%. IL-13 is the central cytokine that is responsible for MCM in asthma through GABA-R- and STAT6-mediated mechanisms involving the calcium-activated chloride channel CLCA. IL-13 is also responsible for the proliferation of AECs by causing cells to produce TGFalpha that acts on the epidermal growth factor (EGF) receptor. Normally, resolution of MCM involves two distinct mechanisms. 1) Some of the metaplastic mucous cells stop the synthesis of mucus and dedifferentiate into Clara or serous cells to reconstitute the epithelium. 2) When proliferation of epithelial cells had occurred, approximately 30% of metaplastic cells are eliminated during the resolution process. Thus, a safe approach to reducing IL-13-induced MCM would involve blocking mucous synthesis and storage, blocking secretion of stored mucus, and eliminating hyperplastic mucous cells. Understanding the molecular mechanisms of each of these processes is necessary for developing effective therapies for reducing mucous hypersecretion in asthma and leading to a repaired epithelium.
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PMID:Regulation of mucous cell metaplasia in bronchial asthma. 1869 Oct 68

Primary cutaneous mucinous carcinoma is a rare adnexal sweat gland neoplasm that mainly affects elderly people. Differential diagnosis includes mammary and gastrointestinal metastatic mucinous carcinoma (MC) and secondary cutaneous involvement by underlying neoplasms. An 83-year-old woman presented with an 8-year history of slow-growing infiltrate plaque in her right hemithorax, with ulceration on supraclavicular area, right upper limb edema and palpable axillary lymphadenopathies. She underwent partial excision of the tumor and local radiotherapy. Imaging studies showed widespread cutaneous dissemination with enlargement of ipsilateral axillary lymph nodes but without evidence of underlying breast cancer. Histopathological examination showed large amounts of mucin in the dermis including small islands of epithelial cells. They stained positive for cytokeratin 7, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15, and c-erbB-2. Lymphatic invasion was demonstrated by D2-40-immunostained sections. A diagnosis of primary cutaneous mucinous carcinoma was made. Our aim was to reevaluate the differential clinical, histopathological, and immunohistochemical criteria for distinguishing primary cutaneous mucinous carcinoma from skin metastases of visceral mucinous carcinoma, especially those arising in breast. We also propose D2-40 as a reliable marker to detect lymphatic invasion that indicates a strong aggressive trend with shorter recurrence-free and predicts nodal metastases.
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PMID:Mucinous carcinoma of the skin: evaluation of lymphatic invasion with D2-40. 1880 1

Matrix metalloproteinases (MMPs), especially MMP-9, have been found to increase the expression of epidermal growth factor (EGF) receptor, a possible regulator of acrolein-induced mucin expression in the airway epithelium. The aim of this study was to investigate whether doxycycline, a tetracycline antibiotic that inhibits MMPs, attenuates mucus production and synthesis of mucin MUC5AC in acrolein-exposed rats. Sprague-Dawley rats were exposed to acrolein aerosol [3.0parts/million (ppm), 6h/day, 12days] and they received 20mg/kg doxycycline daily by gavage, beginning two days before exposure to acrolein until the end of the experiment. The production of mucin glycoproteins and expression of the MMP-9 and MUC5AC genes were measured in rat trachea. The increase in levels of MMP-9 mRNA and protein in airway epithelium after acrolein exposure was accompanied by an increase in MUC5AC mRNA expression. Doxycycline significantly prevented these increases in acrolein-induced expression of MMP-9 and MUC5AC and attenuated mucus production in tracheal epithelium. These results indicate that doxycycline attenuated acrolein-induced mucin synthesis, in part by inhibiting expression of MMP-9. Thus doxycycline may have a prophylactic effect in the treatment of smoking-induced mucus hypersecretion.
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PMID:Doxycycline attenuates acrolein-induced mucin production, in part by inhibiting MMP-9. 2103 64

The immunohistochemical features of 16 cases of papillary cystadenocarcinoma of salivary glands using a panel of monoclonal and polyclonal antibodies were evaluated. The specimens were from patients postoperatively diagnosed as papillary cystadenocarcinoma of salivary glands where the age of the patients ranged from 20-70 years, males were more commonly affected than the females and parotid gland was the most commonly affected site. The cytokeratins detected by MoAb KL1 and K8.12 were positive in all cases showing a heterogeneity in intensity of reaction. A coexpression of vimentin with cytokeratin was found in 10 cases. The tumor cells had a coexpression of S-100 protein and neuron specific enolase (NSE). Glial fibrillary acidic protein (GFAP) was positive in one case with multiple expression of cytokeratins, vimentin NSE, S-100 protein. The polymorphic mucin MAM-6 was positive in all cases and MAM-3 in 8 cases showing different intensity of reaction. The tumor cells were positive for lysozyme (8 cases), lactoferrin (10 cases) and alpha-1-antichymotrypsin (10 cases). The immunoreactive c-erbB-2 oncoprotein on the cell surface membrane was detected in 2 cases. The labeling index of proliferating cell nuclear antigen in the tumor cells ranged from 3.8 to 43.2% (mean 14.2 +/- standard deviation 9.8). Histopathological feature and a heterogeneity of multiple expression of tissue markers may suggest that a population of cells in papillary cystadenocarcinoma may be counterparts of modified myoepithelial cells of pleomorphic adenoma that express epithelial, mesenchymal and neuronal differentiation although the role of myoepithelial cells in the genesis of this tumor is not clear. However, disorganized stratification and malignant transformation of ductal cells may be the most likely possibility in the histogenesis of this tumor.
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PMID:Papillary cystadenocarcinoma of salivary-glands - an immunohistochemical study. 2156 64

Examination of the immuno-overexpression for myc, ras, c-erbB-2 and p53 and the mucin histochemistry of the gastric adenocarcinoma cells at the earlier stages were performed using 12 lesions of the well differentiated tubular adenocarcinomas, less than 1 mm in greatest dimension (G-ade-1), from the pyloric gland or the intermediate area of the surgically resected stomach. The G-ade-1 had a high frequency of expression of oncogene myc (58%) and of the cancer suppressor gene p53 (83%), while almost no expression of ras or c-erbB-2 was observed. All lesions of G-ade-1 were positive for acid mucin staining, and 8/12 lesions (67%) also for sulfomucin, in 4/12 lesions (33%) gastric native mucin was observed. The adjacent mucosa to all G-ade-1 lesions in this study showed chronic gastritis with incomplete intestinal metaplasia. These results suggested that the human gastric differentiated adenocarcinoma developed accompanying the abnormal expression of myc and p53 with reference to intestinal metaplasia, and that these carcinoma cells always had acid mucin, often the colonic native mucin as sulfomucin, and also sometimes gastric native mucin in the earlier stages.
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PMID:Histogenesis of the gastric differentiated adenocarcinoma-expression of oncogene protein products and mucin histochemistry in minute gastric cancer. 2159 79


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