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)

Anaplastic large cell lymphoma (ALCL) is a rare non-Hodgkin, T-cell lymphoma, representing only 2-3% of all lymphoid neoplasm's in adults according to World Health Organization (WHO). CD30 antigen-positive, large neoplastic cells characterize ALCL. We present here a 46-year-old male with pulmonary ALCL previously diagnosed with Hodgkin disease. Microscopically, atypical bi-and multinucleated cells with frequent mitoses were present. The neoplastic cells were large and had clear cytoplasm, large vesicular nuclei, and prominent nucleoli. Immunophenotypic analysis revealed LCA, vimentin and CD30 positivity. ALK immunostaining was negative. Immunohistochemical profile was consistent with ALK negative ALCL. The progression of Hodgkin lymphoma to aggressive non-Hodgkin lymphoma (ALCL in this case) is well known entity. After the diagnosis was established, our patient immediately had been referred to the Department of Hematology in order to get appropriate chemotherapy, necessary in such cases.
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PMID:A case of T/null anaplastic large cell lymphoma arising in lung. 1699 45

Gene expression profiles of invasive breast carcinomas have identified a subgroup of tumours with worse prognosis, which have been called "basal-like". These are characterized by a specific pattern of expression, being estrogen receptor (ER) and HER2 negative, and frequently expressing at least one basal marker such as basal cytokeratins or epidermal growth factor receptor (EGFR). Previously, our group characterized basal-like tumours in a series of invasive breast carcinomas using P-cadherin (P-CD), p63 and cytokeratin 5 (CK5). Based on that study, we hypothesized that those high-grade basal-like invasive carcinomas might have a pre-invasive counterpart, which could be identified using the same approach. A series of 79 ductal carcinomas in situ (DCIS) were classified into distinct subgroups according to their ER, HER2 and basal markers expression. Luminal DCIS expressed ER and constituted 64.6% of the series; the HER2 overexpressing tumours did not express ER and represented 25.3% of the cases, whereas 10.1% lack the expression of ER and HER2 and expressed at least one basal marker (P-CD, CK5, CK14, p63, vimentin and/or EGFR). These basal-like DCIS were mostly high-grade, with comedo-type necrosis, and consistently showed expression of P-CD and CK5. In conclusion, DCIS with a basal-like phenotype represent a small percentage in our series, being P-CD and CK5, the most useful adjunct markers to distinguish this subset of carcinomas in situ of the breast.
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PMID:P-cadherin and cytokeratin 5: useful adjunct markers to distinguish basal-like ductal carcinomas in situ. 1712 7

Multifocal hyperplasia of interstitial cells of Cajal (ICC hyperplasia) is a precursor of hereditary gastrointestinal stromal tumors (GISTs) in patients with germline mutations of c-KIT or PDGFRA, but precursor lesions of sporadic GISTs have not been defined yet. Small hyalinizing stromal tumors of the proximal stomach (referred to in this study as GIST tumorlets) were collected prospectively from 98 consecutive autopsies and additional cases were retrieved from surgical pathology files (total n=57). GIST tumorlets were grossly detectable in 22.5% consecutive autopsies performed in individuals older than 50 years. All lesions were located in the cardia, fundus, or proximal body, and ranged in size from 1 to 10 mm (4 mm). Similar lesions were not detected in the antrum, duodenum, and the remainder of the bowel. Histologically, the spindle cell subtype comprised all cases, with hyalinization and calcification in 57% of cases. The spindle cells were immunohistochemically positive for vimentin, CD117, and CD34. Twenty-four cases yielded sufficient DNA for subsequent molecular analysis, which showed c-KIT mutations in 11 cases (46%) and PDGFRA mutations in 1 case (4%). Sporadic GIST tumorlets of the proximal stomach are common in the general population over the age of 50 years and frequently show somatic c-KIT mutations. GIST tumorlets probably represent the grossly recognizable counterpart of sporadic ICC hyperplasia caused by somatic c-KIT or PDGFRA mutations. Early hyalinization and calcification seems to confer limited growth potential, and complete regression of such lesions is common. GIST tumorlets likely represent preclinical (preneoplastic) lesions that need additional stimuli to evolve into clinical GISTs, raising the possibility of a hyperplasia-neoplasia sequence in the development of sporadic GISTs.
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PMID:Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. 1719 27

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.
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PMID:Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications. 1721 55

Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have similar phenotypic, immunohistochemical and clinical characteristics. SOX2 is an embryonic transcription factor located at chromosome 3q, a region frequently gained in sporadic basal-like and BRCA1 germline mutated tumours. The aim of the study was to establish whether sox2 expression was related to basal-like sporadic breast tumours. Two hundred and twenty-six sporadic node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK5/6, EGFR, vimentin, HER2, ki67, p53 and sox2 using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER/HER2-negative and CK5/6 and/or EGFR-positive. Thirty cases of this series (13.7%) displayed a basal-like phenotype. Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2+ tumours, P<0.001). Moreover, Sox2 showed a statistically significant inverse association with ER and PR (P=0.001 and 0.017, respectively) and direct association with CK5/6, EGFR and vimentin (P=0.022, 0.005 and <0.001, respectively). Sox2 is preferentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/'stem cell' phenotypic characteristics.
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PMID:Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. 1733 50

Penile malignancies are rare in developed countries. The authors present a case of a penile urethral mesenchymal tumor occurring in a 51-year-old Caucasian male and displaying light microscopic, immunohistochemical, and ultrastructural features suggestive of a pacemaker cell type, combined with a lack of diagnostic features of any other established tumor category. The immunohistochemical profile was intensely positive for vimentin, PKC theta, and NSE and weakly positive to nonreactive for CD34 and smooth muscle actin, and entirely negative for CD117 (c-kit), S-100, and other markers. C-kit and PDGFRA gene analysis showed no mutations. Electron microscopy revealed tumor cells with plentiful cytoplasm and cytoplasmic processes/filopodia, both filled with intermediate filaments and occasional solitary focal densities. There were also prominent smooth endoplasmic reticulum cisternae, caveolae, neurosecretory granules, particularly concentrated in cytoplasmic processes, and synaptic-type structures. Poorly formed basal lamina, gap junctions, and intercellular collagen aggregates, consistent with skeinoid-type fibers, were also noted. Interstitial cells with potential pacemaker function have been recently described in the lower urinary tract, including the urethra, and this tumor may be related to this cellular phenotype.
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PMID:Urethral stromal tumor with pacemaker cell phenotype. 1745 99

Gastrointestinal mesenchymal tumours from two Spanish ibex (Capra pyrenaica hispanica) were examined grossly, histologically and immunohistochemically. One neoplasm was a 1.5 kg tan multinodular cavitated mass in the forestomach. The other tumour was a firm mural mass 1.2 cm in diameter in the colon. Microscopically, both tumours were formed mainly by spindle shaped cells arranged in closely packed interlacing fascicles. Neoplastic cells in both tumours labelled positively for KIT (CD117), vimentin and alpha-smooth muscle actin. These findings suggest that both neoplasms were gastrointestinal stromal tumours and most likely to be derived from the interstitial cells of Cajal or their progenitor cells.
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PMID:KIT-positive gastrointestinal stromal tumours in two Spanish ibex (Capra pyrenaica hispanica). 1770 21

There are a number of leukemogenic protein-tyrosine kinases (PTKs) associated with leukemic transformation. Although each is linked with a specific disease their functional activity poses the question whether they have a degree of commonality in their effects upon target cells. Exon array analysis of the effects of six leukemogenic PTKs (BCR/ABL, TEL/PDGFRbeta, FIP1/PDGFRalpha, D816V KIT, NPM/ALK, and FLT3ITD) revealed few common effects on the transcriptome. It is apparent, however, that proteome changes are not directly governed by transcriptome changes. Therefore, we assessed and used a new generation of iTRAQ tagging, enabling eight-channel relative quantification discovery proteomics, to analyze the effects of these six leukemogenic PTKs. Again these were found to have disparate effects on the proteome with few common targets. BCR/ABL had the greatest effect on the proteome and had more effects in common with FIP1/PDGFRalpha. The proteomic effects of the four type III receptor kinases were relatively remotely related. The only protein commonly affected was eosinophil-associated ribonuclease 7. Five of six PTKs affected the motility-related proteins CAPG and vimentin, although this did not correspond to changes in motility. However, correlation of the proteomics data with that from the exon microarray not only showed poor levels of correlation between transcript and protein levels but also revealed alternative patterns of regulation of the CAPG protein by different oncogenes, illustrating the utility of such a combined approach.
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PMID:Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. 1795 28

Mixed germ cell sex cord-stromal tumors (MGSCTs) of the testis are rare in dogs. We describe the histopathology and immunohistochemical characteristics of an MGSCT associated with a Leydig cell tumor in a cryptorchid testis. Histologically, MGSCT consisted of two nodules of seminiferous tubules lined by germ cells and Sertoli cells in variable proportions. Germ cells had variable size and nuclear features, with frequent giant cells. Germ cells were evenly mixed with Sertoli cells or located in the center of tubules. Markers that labeled mainly germ cells and few or no Sertoli or Leydig cells were calretinin, KIT, and PGP 9.5. E-cadherin, GATA-4, inhibin-alpha (INH-alpha), and neuron-specific enolase (NSE) were predominantly detected in Sertoli cells, whereas melan A was particularly expressed in Leydig cells and vimentin in all three cell types. OCT3/4 was not detected in any cell type. Although more cases of canine MGSCT need to be examined, our results suggest that an immunohistochemical panel of E-cadherin, GATA-4, INH-alpha, KIT, NSE, PGP 9.5, and melan A will help distinguish the three main cell types in canine testicular germ cell and sex cord-stromal tumors.
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PMID:Histologic and immunohistochemical characterization of a testicular mixed germ cell sex cord-stromal tumor and a leydig cell tumor in a dog. 1803 10

Keratinocyte growth factor (KGF) and fibroblast growth factor 10 (FGF-10) are stromal-derived growth factors that interact with their epithelial FGFR2 receptors to mediate stromal--epithelial cell interaction within the prostate gland. This study was conducted to compare the development-related mRNA expression of KGF, FGF-10 and their receptor FGFR2 in immature and mature canine prostate glands. In addition, their expression levels were correlated with the differentiation of stromal cells using vimentin as a mesenchymal cell marker. Quantitative mRNA expression was assessed by real-time polymerase chain reaction (PCR) and the results were expressed as relative mRNA expression of the target gene, which was normalized to the GAPDH reference gene. mRNA analysis revealed a differential expression of KGF, FGF-10 and FGFR2 receptor by the prostate glands of immature and mature dogs. The results showed a 7.3- and 9-fold decrease in mRNA expression of KGF and FGF-10 by mature and immature prostate glands respectively. However, there was no significant change in FGFR2 receptor mRNA expression by mature or immature prostate glands. This downregulation of KGF and FGF-10 expression was associated with a 15-fold decrease in vimentin expression. These results indicate that KGF and FGF-10 expression varied according to the differentiation status of stromal cells and might reflect differential developmental requirements of immature and mature canine prostate glands.
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PMID:Development-related expression of KGF and FGF-10 mRNA in the canine prostate gland. 1804 37


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