Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrinomas from 25 patients were examined by immunohistochemistry (IHC) and in situ hybridization histochemistry (ISH). Most patients (84%) presented with the Zollinger-Ellison syndrome. Six had multiple endocrine neoplasia type I (MEN-I). Twelve patients (48%) had duodenal primaries and 11 of 12 of these had metastases to regional lymph nodes and/or liver in spite of the small sizes of the primary tumors (mean size of 0.9 cm). Five patients had pancreatic gastrinomas and eight patients had metastatic tumor in regional lymph nodes or liver at surgery but a primary was not found. IHC and ISH analyses showed that all cases were positive for gastrin protein and 24 of 25 (96%) expressed gastrin mRNA that was easily detected in formalin-fixed, paraffin-embedded tissue sections. Both benign and malignant tumors expressed alpha subunit of human chorionic gonadotropin protein (alpha-HCG). However, only malignant gastrinomas (29%) expressed adrenocorticotropic hormone protein or proopiomelanocortin (POMC) mRNA. ISH and Northern hybridization analysis revealed that chromogranin A mRNA was the most common member of the chromogranin/secretogranin (Cg/Sg) family which was expressed in both benign and malignant gastrinomas. These results indicate that duodenal gastrinomas are common in both sporadic and MEN-1-associated cases, and small duodenal primaries may be associated with extensive regional lymph node and liver metastases. Expression of ACTH/POMC protein and mRNA was consistently associated only with malignant gastrinomas while gastrin protein, gastrin mRNA and Cgs/Sgs mRNAs were readily detected in both benign and malignant gastrinomas.
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PMID:Analysis of gastrinomas by immunohistochemistry and in situ hybridization histochemistry. 128 76

A series of 3 tumourlets (TLs), 81 typical carcinoids (TCs), 14 atypical carcinoids (ACs) (well-differentiated neuroendocrine carcinomas, WDNCs) and 24 small cell-intermediate cell carcinomas (SCC-ICCs) of the lung were studied. Histopathological features were correlated with amine and peptide hormone immunoreactivity and with clinical data. All types of tumours expressed general neuroendocrine (NE) markers: Grimelius positivity and chromogranins were detected more frequently in well-differentiated (TLs, TCs) than in less well differentiated tumours [ACs (WDNCs) and SCC-ICCs] whereas neuron specific enolase (NSE) was prominent in the latter tumours. TLs and peripheral TCs were benign, often showing a paraganglioid pattern and frequently expressing gastrin-releasing peptide (GRP), which is present in the peripheral airways of normal lung. Central TCs were associated with lymph node metastases in 8.5% of the cases, frequently had a trabecular architecture, often associated with human milk fat globule 2 (HMFG2)-positive acinar and rosette-like structures, and were mainly immunostained for the alpha-subunit of human chorionic gonadotrophin (alpha-hCG) and serotonin. ACs (WDNCs) were associated with intrathoracic and/or extrathoracic metastases in 57.1% of the cases with a mortality rate of 35.7%. Their histological and cytological features were intermediate between those of TCs and SCC-ICCs. ACs (WDNCs) expressed serotonin and alpha-hCG less frequently than TCs. All SCC-ICCs were surgically treated and displayed a mortality rate of 91.6% with a mean survival of 10.2 months after operation. These tumours were characterized by high expression of HMFG2 and NSE, while the expression of both orthotopic (serotonin, GRP) and ectopic (ACTH) specific NE substances was very low. Since all TCs (either central or peripheral) had a favourable outcome, while about 36% of ACs (WDNCs) were fatal, the latter seem more appropriately designated "well-differentiated NE carcinomas". The differential diagnosis between different NE tumours of the lung is important and is mainly based on morphology. Both panendocrine and specific immunohistochemical markers are helpful in distinguishing the less aggressive, mostly benign varieties from the more malignant varieties.
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PMID:Differential diagnostic patterns of lung neuroendocrine tumours. A clinico-pathological and immunohistochemical study of 122 cases. 137 78

A case of a medullary carcinoma of the thyroid gland that secreted both calcitonin and adrenocorticotropin (ACTH) is reported. The patient was a 32-year-old man who was referred to the Clinical Center of the National Institutes of Health with radiologic evidence of intrathoracic and hepatic masses accompanied by florid Cushing's syndrome. Serum levels of calcitonin and ACTH were elevated. The thoracic and hepatic masses were resected. The histologic findings were typical of medullary carcinoma of the thyroid with extensive metastases to the liver. The neoplasm had a predominantly solid pattern, and the neoplastic cells were either round or spindled, many with cytologic atypia. Immunohistochemical analysis of fixed, paraffin-embedded sections demonstrated chromogranin, calcitonin, and ACTH in the neoplastic cells. The immunostaining for chromogranin was intense in all of the cells, whereas weaker staining for calcitonin and ACTH was present in scattered cells. Electron microscopy revealed sparse secretory granules in the majority of tumor cells; a minority of neoplastic cells contained numerous granules. We further characterized this neoplasm by performing dual immunohistochemical analysis. This technique clearly demonstrated the presence of ACTH and calcitonin within the same neoplastic cells. Thus, the medullary carcinoma of the thyroid in this patient was the source of ectopic ACTH secretion causing Cushing's syndrome. In addition, this report highlights the value of using double immunostaining to localize both the ACTH and calcitonin within the same cells.
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PMID:Medullary carcinoma of the thyroid as a cause of Cushing's syndrome: a case with ectopic adrenocorticotropin secretion characterized by double enzyme immunostaining. 156 56

Knowledge of clinico-pathological correlations in canine Cushing's disease is rather poor. Therefore we describe, clinically and pathologically, a case of pituitary tumour-dependent Cushing's disease in an 8-year old female cocker spaniel. Based on our results, the tumour was defined as a non-dexamethasone-suppressive, corticotrophic adenocarcinoma characterized by some new findings such as intracerebral metastases of anti-ACTH-labelled tumour cells and combined alpha-, beta- and gamma 3-MSH immunoreactivity in the tumour.
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PMID:A clinico-pathological study of canine Cushing's disease caused by a pituitary carcinoma. 166 39

Thirty-three bronchial carcinoid tumours operated on in a 22-year period are reviewed. They were histologically verified as typical carcinoids with Grimelius' argryophilic staining (25 cases), electron microscopy (6) and immunostaining for synaptophysin (4). Nineteen were endobronchial and 14 peripheral, intraparenchymal tumours. Lymph-node metastases were present at operation in two patients. Two tumours, in patients with Cushing's syndrome, were hormonally active (one secreting ACTH and the other ACTH and calcitonin). There was one case of multiple endocrine neoplasia syndrome, but none of carcinoid syndrome. During follow-up for 5-18 (mean 8.2) years five patients died of unrelated causes. Only one patient showed distant metastasis (after 15 years in salivary gland and a year later in mediastinal fat). Extensive clinical re-examination was performed on 20 patients, and six others were interviewed. All were well but one, who died of uterine cancer 8 weeks later. Typical bronchial carcinoid is concluded to be of low-grade malignancy and suitable for limited pulmonary resection.
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PMID:Bronchial carcinoid: a clinical follow-up study of 33 cases. 166 42

A 53-yr-old man with Cushing's disease was found to have a pituitary carcinoma with metastases to the liver and lung which produced both CRH and ACTH simultaneously. Despite removal of the pituitary tumor, his Cushing's disease worsened. Endocrinological examination then demonstrated elevated plasma CRH and markedly elevated plasma ACTH, beta-lipotropin, and cortisol concentrations, increased urinary 17-hydroxycorticosteroid and 17-ketosteroid excretion, and no suppression of serum cortisol after low or high dose dexamethasone administration. Urinary 17-hydroxycorticosteroid excretion increased in response to metyrapone, and lysine vasopressin elicited a striking increase in plasma ACTH. A computed tomographic scan of abdomen revealed multiple hypodense areas in the liver and bilateral adrenal hyperplasia. Postmortem histological examination revealed a necrotic hemorrhagic pituitary carcinoma with metastases to the liver, lung, and olfactory bulb. Immunohistochemical staining, gel filtration, and Northern blot analysis of liver and lung metastases revealed evidence of the production of both CRH and ACTH in these metastases. We concluded that the patient's pituitary carcinoma produced both CRH and ACTH.
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PMID:Corticotropin-releasing hormone- and adrenocorticotropin-producing pituitary carcinoma with metastases to the liver and lung in a patient with Cushing's disease. 169 98

The Authors report a case of left adrenal mass incidentally discovered by upper abdominal echogram in a 40 year old man. Physical examination showed no signs of hypercortisolism and plasma cortisol and ACTH levels were in the normal range as well as urinary free cortisol. After adrenalectomy, 4 and 8 month follow-up was performed, without clinical, hormonal and TC evolution. Thirteen months later the patient was referred to our department for widespread oedema, hypertension, hypokalemia and alkalosis. These symptoms were associated with dramatically elevated concentrations of plasmatic and free urinary cortisol. TC showed a large mass in the same adrenal region and diffuse hepatic metastases. In spite of mitotane and ketoconazole therapy the patient died few weeks later.
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PMID:[Unusual endocrine behavior in adrenal carcinoma. A case study]. 181 20

Blood levels of carcinoembryonic antigen (CEA), alpha-fetoprotein, ferritin, ACTH. triiodothyronine and thyroxin were measured by radioimmunoassay in 217 cases of lung, hepatopancreatoduodenal and colonic cancer, 61 patients with nontumor pathology of those sites and in 37 healthy controls. CEA proved the most reliable marker of lung and colonic cancer and tumor-related mechanical jaundice, its lowest concentration in 65-100% of cancer patients exceeding the highest levels observed in controls. In the colorectal group, CEA level returned to normal after radical surgery and rose again at recurrence or distant metastases. Ferritin, cortisol and ACTH appeared less efficient.
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PMID:[Tumor markers--a diagnostic and prognostic test]. 185 87

Serotonin-producing pancreatic endocrine tumours are rare neoplasms which in most cases exhibit malignant biological behaviour. These tumours, in the majority of the well-documented cases, are composed of argyrophil- and argentaffin-positive cells which contain large pleomorphic neurosecretory granules. In contrast, argyrophilic non-argentaffin pancreatic endocrine tumours with tumour cells containing round neurosecretory granules are exceptional. In this study we describe such a tumour not associated with clinical evidence of carcinoid syndrome in a 60-year-old woman. Histological examination revealed tumour extension in pancreatic lymphatic vessels and veins but no evidence of locoregional or distant metastases. Ten months after surgery the patient showed no recurrence of the disease. Immunohistochemistry revealed cytoplasmic serotonin production in the tumour cells which were negative for anti-gastrin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and ACTH. This study emphasizes the usefulness of combined ultrastructural and immunohistochemical investigations in order to identify and characterize the rare pancreatic endocrine tumours with serotonin production.
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PMID:Serotonin-producing pancreatic endocrine tumour. Histological, ultrastructural and immunohistochemical study of a case. 196 80

Molecular characterization of neuroendocrine (Merkel cell) carcinoma of the skin. Review of the literature and report of three cases. Although neuroendocrine carcinoma of the skin (NECS) is comparatively a rare clinical-histological entity, numerous morphological and ultrastructural studies have been carried out since the tumor was identificated by Toker (1972). Recently immunocytochemistry has allowed a better molecular characterization (immunophenotype) of this tumor and a more exact diagnosis. The main problem for the pathologist is the differential diagnosis between NECS and skin neoplasms--both primitive and metastatic--which require a more aggressive treatment. Often the classical morphological criteria do not distinguish NECS from non-Hodgkin's lymphoma, amelanotic melanomas, cutaneous metastases of lung small cell carcinoma or of neuroblastoma. The co-expression of cytokeratins and neurofilaments constantly found in NECS, is surely the best differential criterion from non-neuroendocrine carcinomas. Furthermore, the typical paranuclear location of both the intermediate filaments in NECS is a distinctive peculiarity as opposed to lung microcytoma, where cytokeratins and neurofilaments, when present, show widespread perinuclear positivity. Chromogranin A is found only in a small percentage of tumor cells, whilst synthesis of calcitonin, somatostatin, gastrin, ACTH, is very rare. Finally, the lack of common leukocyte antigen (CLA), S-100 protein and vimentin in NECS rules out the diagnoses of lymphoma, melanoma and sarcoma respectively.
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PMID:[Molecular characterization of cutaneous neuroendocrine (Merkel cell) carcinoma. Review of the literature and presentation of a caseload]. 209 Oct 10


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